WO2025054320A1

WO2025054320A1 - Anti-ackr4 antibodies, compositions and uses thereof

Info

Publication number: WO2025054320A1
Application number: PCT/US2024/045377
Authority: WO
Inventors: Courtney BEERS; John Corbin; Vanessa Soros; Pamela ZHANG; Rashmi BANKOTI; Nicole MALANDRO; Kiran Ahluwalia
Original assignee: Tizona Therapeutics
Current assignee: Tizona Therapeutics
Priority date: 2023-09-05
Filing date: 2024-09-05
Publication date: 2025-03-13
Anticipated expiration: 2026-03-05

Abstract

Provided herein are antibodies that selectively bind to ACKR4 and and compositions comprising the antibodies. They may be capable of inhibiting chemokine scavenging; or may be capable of ACKR4 internalization; or may be capable of AKCR4 down-regulation.

Description

1107368.00126 ANTI-ACKR4 ANTIBODIES, COMPOSITIONS COMPRISING ANTI-ACKR4 ANTIBODIES AND METHODS OF USING ANTI-ACKR4 ANTIBODIES RELATED APPLICATIONS [0001] This application claims priority to U.S. provisional application number 63/536,628 filed September 5, 2023, which is incorporated by reference herein in its entirety. FIELD [0002] Provided herein are antibodies with binding specificity for ACKR4 and compositions comprising the antibodies, including pharmaceutical compositions, and kits. Also provided are methods of using anti-ACKR4 antibodies for therapeutic and diagnostic purposes. REFERENCE TO ELECTRONIC SEQUENCE LISTING [0003] The application contains a Sequence Listing which has been submitted electronically in .XML format and is hereby incorporated by reference in its entirety. Said .XML copy, created on September 4, 2024, is named “1107368.00126.xml” and is 106,308 bytes in size. The sequence listing contained in this .XML file is part of the specification and is hereby incorporated by reference herein in its entirety. BACKGROUND [0004] Atypical chemokine recepetor 4 (ACKR4), formerly known as CCRL1 and CCX-CKR, is a protein that in humans is encoded by the ACKR4 gene. ACKR4 is a cell surface receptor with seven transmembrane domains structurally similar to G protein-coupled receptor proteins. ACKR4 is a receptor for C-C type chemokines and has been shown to bind to dendritic cell and T cell-activated chemokines including CCL19, CCL21, and CCL25. [0005] ACKR4 has been found to regulate the availability of chemokines. Specifically, unlike other G-protein coupled receptors, ACKR4 functions as a “scavenger,” internalizizing chemokines and sorting them for lysosomal degradation to limit local and systemic chemokine concentrations. [0006] ACKR4 is an attractive target for regulating chemokine concentration and is also attractive as a therapeutic target. SUMMARY [0007] A first aspect provides an antibody that binds specifically to a human ACKR4. 1107368.00126 The antibody is capable of one or more of inhibition of chemokine scavenging; ACKR4 internalization; and ACKR4 down-regulation. [0008] In some embodiments, the antibody is a monoclonal antibody. In some embodiments, the antibody is a human antibody, a humanized antibody, or a chimeric antibody. In some embodiments, the antibody is a bispecific antibody, a multi-specific antibody, a diabody, or a multivalent antibody. In some embodiments, the antibody is of the IgG1, IgG2, IgG3, IgG4, IgA, or IgM type. In some embodiments, the antibody is an antigen-binding antibody fragment. In some embodiments, the antibody is a Fab fragment, a Fab' fragment, a F(ab')2 fragment, or an Fv fragment. In some embodiments, the antibody is a single chain antibody, a single domain antibody, or a nanobody. [0009] In some embodiments, the isolated antibody comprises, consists of, or consists essentially of a heavy chain variable region (VH) and a light chain variable region (VL), the VH and/or VL comprising 1, 2, 3, 4, 5, or 6 of: a VHCDR1 having the sequence set forth in SEQ ID NOS: 1-5 or SEQ ID NOS: 12-16; a VHCDR2 having the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36; and a VHCDR3 having the sequence set forth in SEQ ID NOS: 45-48; a VLCDR1 having the sequence set forth in SEQ ID NOS: 55-59; a VLCDR2 having the sequence set forth in SEQ ID NOS: 67-70, and a VLCDR3 having the sequence set forth in SEQ ID NOS: 77-81. [0010] AIn some embodiments, the human ACKR4 (hACKR4), comprises, consists of, or consists essentially of a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising: a VHCDR1 having the sequence set forth in SEQ ID NOS: 1-5 or SEQ ID NOS: 12-16, a VHCDR2 having the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, a VHCDR3 having the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising: a VLCDR1 having the sequence set forth in SEQ ID NOS: 55-59, a VLCDR2 having the sequence set forth in SEQ ID NOS: 67-70, and a VLCDR3 having the sequence set forth in SEQ ID NOS: 77-81. [0011] In some embodiments, the isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprises, consists of, or consists essentially of a heavy chain variable region (VH) and/or a light chain variable region (VL), the VH comprising at least one sequence set forth in any of SEQ ID NOS: 89-94 and the VL comprising at least one sequence set forth in any of SEQ ID NOS: 101-106. [0012] In some embodiments, the antibody molecule capable of binding to human 1107368.00126 ACKR4 (hACKR4) comprises, consists of, or consists essentially of a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising 1, 2, or 3 of: a VHCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 1-5 or 12-16, a VHCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, and a VHCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising 1, 2, or 3 of: a VLCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 55-59, a VLCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 67-70, and a VLCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs 77-81. [0013] In some embodiments, the antibody molecule capable of binding to human ACKR4 (hACKR4), comprises, consists of, or consists essentially of a heavy chain variable region (VH) and a light chain variable region (VL), VH comprising 1, 2, or 3 of: a VHCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 1-5 or 12-16, a VHCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, and a VHCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising 1, 2, or 3 of: a VLCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 55-59, a VLCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 67-70, and a VLCDR3 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs 77-81. [0014] In some emboduments, antibody molecule capable of binding to human ACKR4 (hACKR4) comprises, consists of, or consists essentially of a heavy chain and a light chain, the heavy chain comprising one or more molecules having a sequence consisting of one of SEQ ID NOS: 113-120 and the light chain comprising one or more molecules having a sequence consisting of one of SEQ ID NOS: 128-133. [0015] In some embodiments, the antibody molecule capable of binding to human ACKR4 (hACKR4), comprises, consists of, or consists essentially of a heavy chain and a light chain, the heavy chain comprising one or more molecules, the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 113 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 128; the heavy chain comprising one or more molecules, each molecule having a sequence 1107368.00126 consisting of SEQ ID NO: 114 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 129; the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 115 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 130; the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 116 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 131; the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 117 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 130; the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 118 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 132; the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 119 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 133; and the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 120 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 133. [0016] A second aspect provides an isolated nucleic acid encoding an antibody provided herein. In some embodiments, the isolated nucleic acid comprises an expression vector. Some embodiments provide a prokaryotic or eukaryotic host cell transformed with the one or more expression vectors. Some embodiments provide an oncolytic virus encoding the nucleic acid. Some embodiments provide a method for the production of an antibody of the invention comprising the steps of expressing a nucleic acid provided herein in a prokaryotic or eukaryotic host cell and recovering the protein from the cell or the cell culture supernatant. [0017] A third aspect provides a pharmaceutical comprisition comprising any of the antibodies set forth herein. In some embodiments, the pharmaceutical composition is adopted to any suitable route of administration. In some embodiments, the pharmaceutical compistion comprises one or more excipients. Some embodiments further comprise parenteral dosage forms. [0018] A fourth aspect provides a method of treating an individual having a disease or condition comprising administering any of the antibodies set forth herein to an individual in need thereof. In some embodiments, the disease or condition is cancer, autoimmune disease, and infection. 1107368.00126 BRIEF DESCRIPTION OF THE DRAWINGS [0019] FIG.1 provides a table showing recombinant ACKR4 micelle binding, cellular ACKR4 binding, and inhibition of chemokine scavenging by ACKR4 antibodies disclosed herein. [0020] FIG. 2A shows CHO-hACKR4 binding by representative ACKR4 antibodies. FIG.2B shows sensorgram of recombinant ACKR4 micelle binding by representative ACKR4 antibodies. [0021] FIG. 3 shows CHO ACKR4 and ECL mutant cell binding by ACKR4 antibodies disclosed herein. [0022] FIG. 4A and 4B show inhibition of CCL21 scavenging by representative ACKR4 antibodies in AsPC-1 WT and SUIT2 WT cells, respectively. FIG. 4C shows inhibition of CCL19 scavenging by representative ACKR4 antibodies in SUIT2 WT cells. [0023] FIG. 5A shows extracellular luminescence of HiBiT-ACKR4 upon treatment with ACKR4 antibody or control after 15 h. FIG.5B shows % HiBiT-ACKR4 internalization by ACKR4 antibody calculated by: 100 X [1 - (RLU of treatment / RLU of Neg Ctl IgG)]. FIG.5C and 5D show time-dependent % HiBiT-ACKR4 internalization by ACKR4 antibodies disclosed herein. FIG. 5E shows lytic luminescence of HiBiT-ACKR4 upon treatment with ACKR4 antibody or control after 15 h. FIG.5F shows % HiBiT-ACKR4 down-regulation by ACKR4 antibody calculated by: 100 X [1 - (RLU of treatment / RLU of Neg Ctl IgG)]. [0024] FIG.6A shows in vivo detection of 20 ug of ACKR4 antibodies in mouse serum of BALB/c mice after seven days. FIG.6B shows in vivo detection of 5 ug of ACKR4 antibody in mouse serum of huACKR4 KI/muACKR4 KO mice (HO) and muACKR4 wild type mice (WT) after seven days. FIG. 6C shows in vivo detection of 250 ug of ACKR4 antibodies in mouse serum of HO mice after seven days. [0025] FIG. 7A (C57BL/6 mice), 7B [huACKR4 KI/muACKR4 KO mice (HO) and muACKR4 wild type mice (WT)], and 7C (HO mice) show murine CCL19 levels upon in vivo 250 ug ACKR4 antibody treatment after seven days. FIG. 7D (C57BL/6 mice), 7E (HO and WT mice), and 7F (HO mice) show murine CCL21 levels upon in vivo 250 ug ACKR4 antibody treatment after seven days. DETAILED DESCRIPTION 1107368.00126 [0026] Provided herein are antibodies that selectively bind to ACKR4 and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic methods. 1. Definitions [0027] Unless otherwise defined, all terms of art, notations, and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this invention pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a difference over what is generally understood in the art. The techniques and procedures described or referenced herein are generally well understood and commonly employed using conventional methodologies by those skilled in the art, such as, for example, the widely utilized molecular cloning methodologies described in Sambrook et al., Molecular Cloning: A Laboratory Manual 2nd ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY. As appropriate, procedures involving the use of commercially available kits and reagents are generally carried out in accordance with manufacturer defined protocols and/or parameters unless otherwise noted. [0028] As used herein, the singular forms “a,” “an,” and “the” include the plural referents unless the context clearly indicates otherwise. [0029] The term “about” indicates and encompasses an indicated value and a range above and below that value. In certain embodiments, the term “about” indicates the designated value ± 10%, ± 5%, or ± 1%. In certain embodiments, the term “about” indicates the designated value ± one standard deviation of that value. [0030] The term “combinations thereof” includes every possible combination of elements to which the term refers. [0031] The term “immunoglobulin” refers to a class of structurally related proteins generally comprising two pairs of polypeptide chains: one pair of light (L) chains and one pair of heavy (H) chains. In an “intact immunoglobulin,” all four of these chains are interconnected by disulfide bonds. The structure of immunoglobulins has been well characterized. See, e.g., Paul, Fundamental Immunology 7th ed., Ch. 5 (2013) Lippincott Williams & Wilkins, Philadelphia, PA. Briefly, each heavy chain typically comprises a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region typically 1107368.00126 comprises three domains, CH1, CH2, and CH3. Each light chain typically comprises a light chain variable region (V_L) and a light chain constant region. The light chain constant region typically comprises one domain, abbreviated CL. [0032] The term “Atypical chemokine receptor 4” or “ACKR4” describes a receptor for C-C type chemokines. Specifically, ACKR4 has been shown to bind dendritic cell and T cell-activated chemokines including CXCL13, CCL19, CCL20, CCL21, CCL22, and CCL25. ACKR4 has also been shown to act as a chemokine “scavenger” regulating the concentration of chemokines by internalizing and degrading bound chemokines through lysosomal degradation. [0033] The term “antibody” describes a type of immunoglobulin molecule and is used herein in its broadest sense. An antibody specifically includes intact antibodies (e.g., intact immunoglobulins), and antibody fragments and antigen binding proteins. Antibodies comprise at least one antigen-binding domain. One example of an antigen-binding domain is an antigen binding domain formed by a VH-VL dimer. An “ACKR4 antibody,” “anti-ACKR4 antibody,” “ACKR4 Ab,” “ACKR4-specific antibody,” or “anti-ACKR4 Ab” is an antibody, as described herein, which binds specifically to the antigen ACKR4. [0034] The VH and VL regions may be further subdivided into regions of hypervariability (“hypervariable regions (HVRs);” also called “complementarity determining regions” (CDRs)) interspersed with regions that are more conserved. The more conserved regions are called framework regions (FRs). Each V_H and V_L generally comprises three CDRs and four FRs, arranged in the following order (from N-terminus to C-terminus): FR1 - CDR1 - FR2 - CDR2 - FR3 - CDR3 - FR4. The CDRs are involved in antigen binding, and confer antigen specificity and binding affinity to the antibody. See Kabat et al., Sequences of Proteins of Immunological Interest 5th ed. (1991) Public Health Service, National Institutes of Health, Bethesda, MD, incorporated by reference in its entirety. [0035] The light chain from any vertebrate species can be assigned to one of two types, called kappa and lambda, based on the sequence of the constant domain. [0036] The heavy chain from any vertebrate species can be assigned to one of five different classes (or isotypes): IgA, IgD, IgE, IgG, and IgM. These classes are also designated α, δ, ε, γ, and µ, respectively. The IgG and IgA classes are further divided into subclasses on the basis of differences in sequence and function. Humans express the following subclasses: IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. 1107368.00126 [0037] The amino acid sequence boundaries of a CDR can be determined by one of skill in the art using any of a number of known numbering schemes, including those described by Kabat et al., supra (“Kabat” numbering scheme); Al-Lazikani et al., 1997, J. Mol. Biol., 273:927-948 (“Chothia” numbering scheme); MacCallum et al., 1996, J. Mol. Biol. 262:732- 745 (“Contact” numbering scheme); Lefranc et al., Dev. Comp. Immunol., 2003, 27:55-77 (“IMGT” numbering scheme); and Honegge and Plückthun, J. Mol. Biol., 2001, 309:657-70 (“AHo” numbering scheme), each of which is incorporated by reference in its entirety. [0038] Table 1 provides the positions of CDR-L1, CDR-L2, CDR-L3, CDR-H1, CDR- H2, and CDR-H3 as identified by the Kabat and Chothia schemes. For CDR-H1, residue numbering is provided using both the Kabat and Chothia numbering schemes. [0039] Unless otherwise specified, the numbering scheme used for identification of a particular CDR herein is the Kabat/Chothia numbering scheme. Where the residues encompassed by these two numbering schemes diverge, the numbering scheme is specified as either Kabat or Chothia. Table 1. Residues in CDRs according to Kabat and Chothia numbering schemes. CDR Kabat Chothia L1 L24-L34 L24-L34 L2 L50-L56 L50-L56 L3 L89-L97 L89-L97 H_{1 (Kabat Numbering)} ^H31-H35B _{H26-H32 or H34*} H1 (Chothia Numbering) H31-H35 H26-H32 H2 H50-H65 H52-H56 H3 H95-H102 H95-H102 * The C-terminus of CDR-H1, when numbered using the Kabat numbering convention, varies between H32 and H34, depending on the length of the CDR. [0040] The “EU numbering scheme” is generally used when referring to a residue in an antibody heavy chain constant region (e.g., as reported in Kabat et al., supra). Unless stated otherwise, the EU numbering scheme is used to refer to residues in antibody heavy chain constant regions described herein. [0041] An “antibody fragment” comprises a portion of an intact antibody, such as the antigen binding or variable region of an intact antibody. Antibody fragments include, for example, Fv fragments, Fab fragments, F(ab′)₂ fragments, Fab′ fragments, scFv (sFv) fragments, and scFv-Fc fragments. [0042] “Fv” fragments comprise a non-covalently-linked dimer of one heavy chain 1107368.00126 variable domain and one light chain variable domain. [0043] “Fab” fragments comprise, in addition to the heavy and light chain variable domains, the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab fragments may be generated, for example, by papain digestion of a full-length antibody. [0044] “F(ab′)2” fragments contain two Fab′ fragments joined, near the hinge region, by disulfide bonds. F(ab′)₂ fragments may be generated, for example, by pepsin digestion of an intact antibody. The F(ab′) fragments can be dissociated, for example, by treatment with ß- mercaptoethanol. [0045] “Single-chain Fv” or “sFv” or “scFv” antibody fragments comprise a V_H domain and a VL domain in a single polypeptide chain. The VH and VL are generally linked by a peptide linker. See Plückthun A. (1994). Antibodies from Escherichia coli. In Rosenberg M. & Moore G.P. (Eds.), The Pharmacology of Monoclonal Antibodies vol. 113 (pp. 269-315). Springer-Verlag, New York, incorporated by reference in its entirety. “scFv-Fc” fragments comprise an scFv attached to an Fc domain. For example, an Fc domain may be attached to the C-terminal of the scFv. The Fc domain may follow the VH or VL, depending on the orientation of the variable domains in the scFv (i.e., V_H-V_L or V_L-V_H). Any suitable Fc domain known in the art or described herein may be used. [0046] The term “monoclonal antibody” refers to an antibody from a population of substantially homogeneous antibodies. A population of substantially homogeneous antibodies comprises antibodies that are substantially similar and that bind the same epitope(s), except for variants that may normally arise during production of the monoclonal antibody. Such variants are generally present in only minor amounts. A monoclonal antibody is typically obtained by a process that includes the selection of a single antibody from a plurality of antibodies. For example, the selection process can be the selection of a unique clone from a plurality of clones, such as a pool of hybridoma clones, phage clones, yeast clones, bacterial clones, or other recombinant DNA clones. The selected antibody can be further altered, for example, to improve affinity for the target (“affinity maturation”), to humanize the antibody, to improve its production in cell culture, and/or to reduce its immunogenicity in a subject. [0047] The term “chimeric antibody” refers to an antibody in which a portion of the heavy and/or light chain is derived from a particular source or species, while the remainder of the heavy and/or light chain is derived from a different source or species. 1107368.00126 [0048] “Humanized” forms of non-human antibodies are chimeric antibodies that contain minimal sequence derived from the non-human antibody. A humanized antibody is generally a human immunoglobulin (recipient antibody) in which residues from one or more CDRs are replaced by residues from one or more CDRs of a non-human antibody (donor antibody). The donor antibody can be any suitable non-human antibody, such as a mouse, rat, rabbit, chicken, or non-human primate antibody having a desired specificity, affinity, or biological effect. In some instances, selected framework region residues of the recipient antibody are replaced by the corresponding framework region residues from the donor antibody. Humanized antibodies may also comprise residues that are not found in either the recipient antibody or the donor antibody. Such modifications may be made to further refine antibody function. For further details, see Jones et al., Nature, 1986, 321:522-525; Riechmann et al., Nature, 1988, 332:323-329; and Presta, Curr. Op. Struct. Biol., 1992, 2:593-596, each of which is incorporated by reference in its entirety. [0049] A “human antibody” is one which possesses an amino acid sequence corresponding to that of an antibody produced by a human or a human cell, or derived from a non-human source that utilizes a human antibody repertoire or human antibody-encoding sequences (e.g., obtained from human sources or designed de novo). Human antibodies specifically exclude humanized antibodies. [0050] An “isolated antibody” is one that has been separated and/or recovered from a component of its natural environment. Components of the natural environment may include enzymes, hormones, and other proteinaceous or nonproteinaceous materials. In some embodiments, an isolated antibody is purified to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example by use of a spinning cup sequenator. In some embodiments, an isolated antibody is purified to homogeneity by gel electrophoresis (e.g., SDS-PAGE) under reducing or nonreducing conditions, with detection by Coomassie blue or silver stain. An isolated antibody includes an antibody in situ within recombinant cells, since at least one component of the antibody's natural environment is not present. In some embodiments, an isolated antibody is prepared by at least one purification step. [0051] In some embodiments, an isolated antibody is purified to at least 80%, 85%, 90%, 95%, or 99% by weight. In some embodiments, an isolated antibody is provided as a solution comprising at least 85%, 90%, 95%, 98%, 99% to 100% by weight of an antibody, the remainder of the weight comprising the weight of other solutes dissolved in the solvent. 1107368.00126 [0052] “Affinity” refers to the strength of the sum total of non-covalent interactions between a single binding site of a molecule (e.g., an antibody) and its binding partner (e.g., an antigen). Unless indicated otherwise, as used herein, “binding affinity” refers to intrinsic binding affinity, which reflects a 1:1 interaction between members of a binding pair (e.g., antibody and antigen). The affinity of a molecule X for its partner Y can generally be represented by the dissociation constant (K_D). Affinity can be measured by common methods known in the art, including those described herein. Affinity can be determined, for example, using surface plasmon resonance (SPR) technology, such as a Biacore^® instrument, or using bio-layer interferometry technology, such as an Octet^® instrument. [0053] With regard to the binding of an antibody to a target molecule, the terms “specific binding,” “specifically binds to,” “specific for,” “selectively binds,” and “selective for” a particular antigen (e.g., a polypeptide target) or an epitope on a particular antigen mean binding that is measurably different from a non-specific or non-selective interaction. Specific binding can be measured, for example, by determining binding of a molecule compared to binding of a control molecule. Specific binding can also be determined by competition with a control molecule that is similar to the target, such as an excess of non-labeled target. In that case, specific binding is indicated if the binding of the labeled target to a probe is competitively inhibited by the excess non-labeled target. [0054] The term “kd” (sec⁻¹), as used herein, refers to the dissociation rate constant of a particular antibody-antigen interaction. This value is also referred to as the k_off value. [0055] The term “k_a” (M⁻¹×sec⁻¹), as used herein, refers to the association rate constant of a particular antibody-antigen interaction. This value is also referred to as the kon value. [0056] The term “KD” (M), as used herein, refers to the dissociation equilibrium constant of a particular antibody-antigen interaction. K_D = k_d/k_a. [0057] The term “KA” (M⁻¹), as used herein, refers to the association equilibrium constant of a particular antibody-antigen interaction. KA = ka/kd. [0058] An “affinity matured” antibody is one with one or more alterations in one or more CDRs or FRs that result in an improvement in the affinity of the antibody for its antigen, compared to a parent antibody which does not possess the alteration(s). In one embodiment, an affinity matured antibody has nanomolar or picomolar affinity for the target antigen. Affinity matured antibodies may be produced using a variety of methods known in the art. For example, Marks et al. (Bio/Technology, 1992, 10:779-783, incorporated by reference in its 1107368.00126 entirety) describes affinity maturation by VH and VL domain shuffling. Random mutagenesis of CDR and/or framework residues is described by, for example, Barbas et al. (Proc. Nat. Acad. Sci. U.S.A., 1994, 91:3809-3813); Schier et al., Gene, 1995, 169:147-155; Yelton et al., J. Immunol., 1995, 155:1994-2004; Jackson et al., J. Immunol., 1995, 154:3310-33199; and Hawkins et al, J. Mol. Biol., 1992, 226:889-896, each of which is incorporated by reference in its entirety. [0059] When used herein in the context of two or more antibodies, the term “competes with” or “cross-competes with” indicates that the two or more antibodies compete for binding to an antigen (e.g., ACKR4). In one exemplary assay, ACKR4 is coated on a plate and allowed to bind a first antibody, after which a second, labeled antibody is added. If the presence of the first antibody reduces binding of the second antibody, then the antibodies compete. The term “competes with” also includes combinations of antibodies where one antibody reduces binding of another antibody, but where no competition is observed when the antibodies are added in the reverse order. However, in some embodiments, the first and second antibodies inhibit binding of each other, regardless of the order in which they are added. In some embodiments, one antibody reduces binding of another antibody to its antigen by at least 50%, at least 60%, at least 70%, at least 80%, or at least 90%. [0060] The term “epitope” means a portion of an antigen capable of specific binding to an antibody. Epitopes frequently consist of surface-accessible amino acid residues and/or sugar side chains and may have specific three-dimensional structural characteristics, as well as specific charge characteristics. Conformational and non-conformational epitopes are distinguished in that the binding to the former but not the latter is lost in the presence of denaturing solvents. An epitope may comprise amino acid residues that are directly involved in the binding, and other amino acid residues, which are not directly involved in the binding. The epitope to which an antibody binds can be determined using known techniques for epitope determination such as, for example, testing for antibody binding to ACKR4 variants with different point-mutations. [0061] Percent “identity” between a polypeptide sequence and a reference sequence, is defined as the percentage of amino acid residues in the polypeptide sequence that are identical to the amino acid residues in the reference sequence, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Alignment for purposes of determining percent amino acid sequence identity can be achieved in various ways that are within the skill in the art, for instance, using publicly available computer software 1107368.00126 such as BLAST, BLAST-2, ALIGN, MEGALIGN (DNASTAR), CLUSTALW, or CLUSTAL OMEGA software. Those skilled in the art can determine appropriate parameters for aligning sequences, including any algorithms needed to achieve maximal alignment over the full length of the sequences being compared. [0062] A “conservative substitution” or a “conservative amino acid substitution,” refers to the substitution of one or more amino acids with one or more chemically or functionally similar amino acids. Conservative substitution tables providing similar amino acids are well known in the art. Polypeptide sequences having such substitutions are known as “conservatively modified variants.” By way of example, the following groups of amino acids are considered conservative substitutions for one another. Acidic Residues D and E Basic Residues K, R, and H

Group A A and G Group B D and E Group C N and Q Group D R, K, and H 1107368.00126 Group E I, L, M, V Group F F, Y, and W

Proteins: Structures and Molecular Properties 2nd ed. (1993) W. H. Freeman & Co., New York, NY. An antibody generated by making one or more conservative substitutions of amino acid residues in a parent antibody is referred to as a “conservatively modified variant.” [0064] The term “amino acid” refers to the twenty common naturally occurring amino acids. Naturally occurring amino acids include alanine (Ala; A), arginine (Arg; R), asparagine (Asn; N), aspartic acid (Asp; D), cysteine (Cys; C); glutamic acid (Glu; E), glutamine (Gln; Q), Glycine (Gly; G); histidine (His; H), isoleucine (Ile; I), leucine (Leu; L), lysine (Lys; K), methionine (Met; M), phenylalanine (Phe; F), proline (Pro; P), serine (Ser; S), threonine (Thr; T), tryptophan (Trp; W), tyrosine (Tyr; Y), and valine (Val; V). [0065] “Treating” or “treatment” of any disease or disorder refers, in certain embodiments, to ameliorating a disease or disorder that exists in a subject. In another embodiment, “treating” or “treatment” includes ameliorating at least one physical parameter, which may be indiscernible by the subject. In yet another embodiment, “treating” or “treatment” includes modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom) or physiologically (e.g., stabilization of a physical parameter) or both. In yet another embodiment, “treating” or “treatment” includes delaying or preventing the onset of the disease or disorder. [0066] As used herein, the term “therapeutically effective amount” or “effective amount” refers to an amount of an antibody or composition that when administered to a subject is effective to treat a disease or disorder. [0067] As used herein, the term “subject” means a mammalian subject. Exemplary subjects include, but are not limited to humans, monkeys, dogs, cats, mice, rats, cows, horses, camels, avians, goats and sheep. In certain embodiments, the subject is a human. In some embodiments, the subject has cancer, an autoimmune disease or condition, and/or an infection that can be treated with an antibody provided herein. In some embodiments, the subject is a human that is suspected to have cancer, an autoimmune disease or condition, and/or an acute infection and chronic infection. 1107368.00126 2. Antibodies [0068] A first aspect provides an antibodies that selectively bind human ACKR4. In some embodiments, the antibody selectively binds to the extracellular domain of human ACKR4. [0069] In some embodiments, the antibody has one or more CDRs having particular lengths, in terms of the number of amino acid residues. In some embodiments, the Chothia CDR-H1 of the antibody is 6, 7, 8, or 9 residues in length. In some embodiments, the Kabat CDR-H1 of the antibody is 4, 5, 6, or 7 residues in length. In some embodiments, the Chothia CDR-H2 of the antibody is 5, 6, or 7 residues in length. In some embodiments, the Kabat CDR-H2 of the antibody is 15, 16, 17, or 18 residues in length. In some embodiments, the Kabat/Chothia CDR-H3 of the antibody is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 residues in length. [0070] In some embodiments, the Kabat/Chothia CDR-L1 of the antibody is 9, 10, 11, 12, 13, 14, 15, or 16 residues in length. In some embodiments, the Kabat/Chothia CDR-L2 of the antibody is 6, 7, or 8 residues in length. In some embodiments, the Kabat/Chothia CDR- L3 of the antibody is 8, 9, 10, 11, or 12 residues in length. [0071] In some embodiments, the antibody comprises a light chain. In some embodiments, the light chain is a kappa light chain. In some embodiments, the light chain is a lambda light chain. [0072] In some embodiments, the antibody comprises a heavy chain. In some embodiments, the heavy chain is an IgA. In some embodiments, the heavy chain is an IgD. In some embodiments, the heavy chain is an IgE. In some embodiments, the heavy chain is an IgG. In some embodiments, the heavy chain is an IgM. In some embodiments, the heavy chain is an IgG1. In some embodiments, the heavy chain is an IgG2. In some embodiments, the heavy chain is an IgG3. In some embodiments, the heavy chain is an IgG4. In some embodiments, the heavy chain is an IgA1. In some embodiments, the heavy chain is an IgA2. [0073] In some embodiments, the antibody is an antibody fragment. In some embodiments, the antibody fragment is an Fv fragment. In some embodiments, the antibody fragment is a Fab fragment. In some embodiments, the antibody fragment is a F(ab′)2 fragment. In some embodiments, the antibody fragment is a Fab′ fragment. In some embodiments, the antibody fragment is an scFv (sFv) fragment. In some embodiments, the antibody fragment is an scFv-Fc fragment. [0074] In some embodiments, the antibody is a monoclonal antibody. In some 1107368.00126 embodiments, the antibody is a polyclonal antibody. [0075] In some embodiments, the antibody is a chimeric antibody. In some embodiments, the antibody is a humanized antibody. In some embodiments, the antibody is a human antibody. [0076] In some embodiments, the antibody is an affinity matured antibody. In some embodiments, the antibody is an affinity matured antibody derived from an illustrative sequence provided in this disclosure. [0077] In some embodiments, the antibody binds to ACKR4 and causes internalization of ACKR4. In some embodiments, the antibody binds to ACKR4 and causes degradation of ACKR4. In some embodiments, the antibody binds ACKR4 inhibiting the chemokine scavenging function of ACKR4. [0078] The antibodies provided herein may be useful for the treatment of a variety of diseases and conditions, including cancers, autoimmune diseases, and infections. In some embodiments, the antibody inhibits ACKR4 chemokine scavenging. In some embodiments, the antibody internalizes and down-regulates ACKR4. [0079] In some embodiments, the antibody competes or is capable of competing for binding to human ACKR4 with another antibody or chemokine. In some embodiments, the antibody comprises or consists an antibody that is capable of competing for binding to human ACKR4 with a reference antibody, wherein the reference antibody binds to an epitope comprising position Cys262-Glu289, Met1-Val42, Tyr176-Gln201, and/or Met1-Lys41 of SEQ ID NO: 147 on a human ACKR4 polypeptide. In some embodiments, the antibody and the reference antibody cross-compete or are capable of cross-competing for binding to human ACKR4 with another antibody or chemokine. [0080] In some embodiments, the antibody binds to an epitope of SEQ ID NO: 147 on a human ACKR4 polypeptide. In some embodiments, the epitope comprises or consists of a contiguous or non-contiguous span of amino acids of the sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope comprises a sequence that is identical or corresponds to a sequence that is within the sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope has a sequence that has a 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identity to a sequence that is within the sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions from a sequence that is within the sequence set forth in forth in SEQ ID NO: 147. In some embodiments, the epitope has 1, 2, or 3 1107368.00126 substitutions from residues a sequence that is within the sequence set forth in SEQ ID NO: 147. 2.1. CDR-H3 Sequences [0081] In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 45. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 46. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 47. In some embodiments, the antibody comprises a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 48. [0082] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-H3 sequence provided in this disclosure. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences provided in this disclosure. In some embodiments, the CDR- H3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.2. V_H Sequences Comprising Illustrative CDRs [0083] In some embodiments, the antibody comprises a VH sequence comprising one or more CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative CDR-H sequences provided in this disclosure, and variants thereof. 2.2.1. V_H Sequences Comprising Illustrative Kabat CDRs [0084] In some embodiments, the antibody comprises a V_H sequence comprising one or more Kabat CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative Kabat CDR-H sequences provided in this disclosure, and variants thereof. 2.2.1.1.Kabat CDR-H3 [0085] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 45. In some embodiments, the antibody comprises a VH sequence 1107368.00126 comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 46. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 47. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR- H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 48. . 2.2.1.2.Kabat CDR-H2 [0086] In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 23-25. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 23. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 24. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 25. 2.2.1.3.Kabat CDR-H1 [0087] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-5. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 1. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 2. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 3. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 4. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 5. 2.2.1.4.Kabat CDR-H3 + Kabat CDR-H2 [0088] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48 and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 23-25. In some 1107368.00126 embodiments, the Kabat CDR-H3 sequence and the Kabat CDR-H2 sequence are both from a single illustrative V_H sequence provided in this disclosure. For example, in some embodiments, the Kabat CDR-H3 and Kabat CDR-H2 are both from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 2.2.1.5.Kabat CDR-H3 + Kabat CDR-H1 [0089] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48, and a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-5. In some embodiments, the Kabat CDR-H3 sequence and the Kabat CDR-H1 sequence are both from a single illustrative V_H sequence provided in this disclosure. For example, in some embodiments, the Kabat CDR-H3 and Kabat CDR-H1 are both from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 2.2.1.6.Kabat CDR-H1 + Kabat CDR-H2 [0090] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-5 and a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 23-25. In some embodiments, the Kabat CDR-H1 sequence and the Kabat CDR-H2 sequence are both from a single illustrative V_H sequence provided in this disclosure. For example, in some embodiments, the Kabat CDR-H1 and Kabat CDR-H2 are both from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 2.2.1.7.Kabat CDR-H1 + Kabat CDR-H2 + Kabat CDR-H3 [0091] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 1-5, a Kabat CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 23-25, and a Kabat CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48. In some embodiments, the Kabat CDR-H1 sequence, Kabat CDR-H2 sequence, and Kabat CDR-H3 sequence are all from a single illustrative VH sequence provided in this disclosure. For example, in some embodiments, the Kabat CDR-H1, Kabat CDR-H2, and Kabat CDR-H3 are all from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 1107368.00126 [0092] In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 1, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 2, a Kabat CDR-H2 sequence comprising SEQ ID NO: 24, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 46. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 3, a Kabat CDR-H2 sequence comprising SEQ ID NO: 25, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 47. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 4, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45. In some embodiments, the antibody comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 3, a Kabat CDR-H2 sequence comprising SEQ ID NO: 25, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 48. In some embodiments, the antibody comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 5, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45. 2.2.1.8.Variants of V_H Sequences Comprising Illustrative Kabat CDRs [0093] In some embodiments, the V_H sequences provided herein comprise a variant of an illustrative Kabat CDR-H3, CDR-H2, and/or CDR-H1 sequence provided in this disclosure. [0094] In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H3 sequence provided in this disclosure. In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Kabat CDR-H3 sequences provided in this disclosure. In some embodiments, the Kabat CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [0095] In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H2 sequence provided in this disclosure. In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity 1107368.00126 with any of the illustrative Kabat CDR-H2 sequences provided in this disclosure. In some embodiments, the Kabat CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [0096] In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a variant of an illustrative Kabat CDR-H1 sequence provided in this disclosure. In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Kabat CDR-H1 sequences provided in this disclosure. In some embodiments, the Kabat CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Kabat CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.2.2. V_H Sequences Comprising Illustrative Chothia CDRs [0097] In some embodiments, the antibody comprises a V_H sequence comprising one or more Chothia CDR-H sequences comprising, consisting of, or consisting essentially of one or more illustrative Chothia CDR-H sequences provided in this disclosure, and variants thereof. 2.2.2.1.Chothia CDR-H3 [0098] In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 45. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 46. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 47. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR- H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 48. 2.2.2.2.Chothia CDR-H2 [0099] In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence 1107368.00126 selected from SEQ ID NOS: 34-36. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 34. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 35. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 36. 2.2.2.3.Chothia CDR-H1 [00100] In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 12-16. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 12. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 13. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 14. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR- H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 15. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 16. 2.2.2.4.Chothia CDR-H3 + Chothia CDR-H2 [00101] In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48, and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 34-36. In some embodiments, the Chothia CDR-H3 sequence and the Chothia CDR-H2 sequence are both from a single illustrative V_H sequence provided in this disclosure. For example, in some embodiments, the Chothia CDR-H3 and Chothia CDR-H2 are both from a single illustrative V_H sequence selected from SEQ ID NOS: 89-94. 2.2.2.5.Chothia CDR-H3 + Chothia CDR-H1 [00102] In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48, and a Chothia CDR-H1 sequence comprising, consisting 1107368.00126 of, or consisting essentially of a sequence selected from SEQ ID NOS: 12-16. In some embodiments, the Chothia CDR-H3 sequence and the Chothia CDR-H1 sequence are both from a single illustrative VH sequence provided in this disclosure. For example, in some embodiments, the Chothia CDR-H3 and Chothia CDR-H1 are both from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 2.2.2.6.Chothia CDR-H1 + Chothia CDR-H2 [00103] In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 12-16 and a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 34-36. In some embodiments, the Chothia CDR-H1 sequence and the Chothia CDR-H2 sequence are both from a single illustrative VH sequence provided in this disclosure. For example, in some embodiments, the Chothia CDR-H1 and Chothia CDR-H2 are both from a single illustrative VH sequence selected from SEQ ID NOS: 89-94. 2.2.2.7.Chothia CDR-H1 + Chothia CDR-H2 + Chothia CDR-H3 [00104] In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 12-16, a Chothia CDR-H2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 34-36, and a Chothia CDR- H3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 45-48. In some embodiments, the Chothia CDR-H1 sequence, Chothia CDR- H2 sequence, and Chothia CDR-H3 sequence are all from a single illustrative V_H sequence provided in this disclosure. For example, in some embodiments, the Chothia CDR-H1, Chothia CDR-H2, and Chothia CDR-H3 are all from a single illustrative V_H sequence selected from SEQ ID NOS: 89-94. [00105] In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 35, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 46. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 36, and a Chothia CDR-H3 1107368.00126 sequence comprising SEQ ID NO: 47. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 15, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45. In some embodiments, the antibody comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 36, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 48. In some embodiments, the antibody comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 16, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45. 2.2.2.8.Variants of V_H Sequences Comprising Illustrative Chothia CDRs [00106] In some embodiments, the V_H sequences provided herein comprise a variant of an illustrative Chothia CDR-H3, CDR-H2, and/or CDR-H1 sequence provided in this disclosure. [00107] In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H3 sequence provided in this disclosure. In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H3 sequences provided in this disclosure. In some embodiments, the Chothia CDR-H3 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [00108] In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a variant of an illustrative Chothia CDR-H2 sequence provided in this disclosure. In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H2 sequences provided in this disclosure. In some embodiments, the Chothia CDR-H2 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [00109] In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, 1107368.00126 or consists essentially of a variant of an illustrative Chothia CDR-H1 sequence provided in this disclosure. In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative Chothia CDR-H1 sequences provided in this disclosure. In some embodiments, the Chothia CDR-H1 sequence comprises, consists of, or consists essentially of any of the illustrative Chothia CDR-H1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.3. V_H Sequences [00110] In some embodiments, the antibody comprises a VH sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 89-94. In some embodiments, the antibody comprises a VH sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 89. In some embodiments, the antibody comprises a V_H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 90. In some embodiments, the antibody comprises a V_H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 91. In some embodiments, the antibody comprises a VH sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 92. In some embodiments, the antibody comprises a VH sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 93. In some embodiments, the antibody comprises a V_H sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 94. 2.3.1. Variants of V_H Sequences [00111] In some embodiments, the V_H sequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative VH sequence provided in this disclosure. [00112] In some embodiments, the VH sequence comprises, consists of, or consists essentially of a variant of an illustrative V_H sequence provided in this disclosure. In some embodiments, the VH sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.5% identity with any of the illustrative VH sequences provided in this disclosure. [00113] In some embodiments, the VH sequence comprises, consists of, or consists essentially of any of the illustrative V_H sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or 1107368.00126 fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.4. VL Sequences Comprising Illustrative CDRs [00114] In some embodiments, the antibody comprises a VL sequence comprising one or more CDR-L sequences comprising, consisting of, or consisting essentially of one or more illustrative CDR-L sequences provided in this disclosure, and variants thereof. 2.5. CDR-L3 Sequences [00115] In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 77-81. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 77. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 78. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 79. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 80. In some embodiments, the antibody comprises a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 81. [00116] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR- L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.5.1. CDR-L2 [00117] In some embodiments, the antibody comprises a VL sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 67-70. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 67. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 68. In some 1107368.00126 embodiments, the antibody comprises a VL sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 69. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L2 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 70. 2.5.2. CDR-L1 [00118] In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 55-59. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 55. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 56. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 57. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 58. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 59. 2.5.3. CDR-L3 + CDR-L2 [00119] In some embodiments, the antibody comprises a VL sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 77-81 and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 67-70. In some embodiments, the CDR- L3 sequence and the CDR-L2 sequence are both from a single illustrative VL sequence provided in this disclosure. For example, in some embodiments, the CDR-L3 and CDR-L2 are both from a single illustrative VL sequence selected from SEQ ID NOS: 101-106. 2.5.4. CDR-L3 + CDR-L1 [00120] In some embodiments, the antibody comprises a V_L sequence comprising a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 77-81 and a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 55-59. In some embodiments, the CDR- L3 sequence and the CDR-L1 sequence are both from a single illustrative VL sequence provided in this disclosure. For example, in some embodiments, the CDR-L3 and CDR-L1 are both from a single illustrative VL sequence selected from SEQ ID NOS: 101-106. 1107368.00126 2.5.5. CDR-L1 + CDR-L2 [00121] In some embodiments, the antibody comprises a V_L sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 55-59 and a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 67-70. In some embodiments, the CDR- L1 sequence and the CDR-L2 sequence are both from a single illustrative V_L sequence provided in this disclosure. For example, in some embodiments, the CDR-L1 and CDR-L2 are both from a single illustrative V_L sequence selected from SEQ ID NOS: 101-106. 2.5.6. CDR-L1 + CDR-L2 + CDR-L3 [00122] In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 55-59, a CDR-L2 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 67-70, and a CDR-L3 sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 77-81. In some embodiments, the CDR-L1 sequence, CDR-L2 sequence, and CDR-L3 sequence are all from a single illustrative VL sequence provided in this disclosure. For example, in some embodiments, the CDR-L1, CDR-L2, and CDR-L3 are all from a single illustrative VL sequence selected from SEQ ID NOS: 101-106. [00123] In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 67, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 56, a CDR-L2 sequence comprising SEQ ID NO: 68, and a CDR-L3 sequence SEQ ID NO: 78. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 57, a CDR-L2 sequence comprising SEQ ID NO: 69, and a CDR-L3 sequence SEQ ID NO: 79. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 58, a CDR- L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 80. In some embodiments, the antibody comprises a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 59, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 81. 1107368.00126 2.5.7. Variants of V_L Sequences Comprising Illustrative CDR-Ls [00124] In some embodiments, the V_L sequences provided herein comprise a variant of an illustrative CDR-L3, CDR-L2, and/or CDR-L1 sequence provided in this disclosure. [00125] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [00126] In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L2 sequence provided in this disclosure. In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L2 sequences provided in this disclosure. In some embodiments, the CDR-L2 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L2 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [00127] In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L1 sequence provided in this disclosure. In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L1 sequences provided in this disclosure. In some embodiments, the CDR-L1 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L1 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.6. V_L Sequences [00128] In some embodiments, the antibody comprises a VL sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 101-106. In some embodiments, the antibody comprises a VL sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 101. In some embodiments, the antibody comprises a 1107368.00126 VL sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 102. In some embodiments, the antibody comprises a V_L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 103. In some embodiments, the antibody comprises a VL sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 104. In some embodiments, the antibody comprises a VL sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 105. In some embodiments, the antibody comprises a V_L sequence comprising, consisting of, or consisting essentially of SEQ ID NO: 106. 2.6.1. Variants of VL Sequences [00129] In some embodiments, the V_L sequences provided herein comprise, consist of, or consist essentially of a variant of an illustrative VL sequence provided in this disclosure. [00130] In some embodiments, the VL sequence comprises, consists of, or consists essentially of a variant of an illustrative V_L sequence provided in this disclosure. In some embodiments, the VL sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity with any of the illustrative VL sequences provided in this disclosure. [00131] In some embodiments, the VL sequence comprises, consists of, or consists essentially of any of the illustrative V_L sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.7. Pairs 2.7.1. CDR-H3 – CDR-L3 Pairs [00132] In some embodiments, the antibody comprises a CDR-H3 sequence and a CDR- L3 sequence. In some embodiments, the CDR-H3 sequence is part of a VH and the CDR-L3 sequence is part of a V_L. [00133] In some embodiments, the CDR-H3 sequence is a CDR-H3 sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 45-48 and the CDR-L3 sequence is a CDR-L3 sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 77-81. [00134] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 45 and the CDR- L3 sequence is selected from SEQ ID NOS: 77-81. In some embodiments, the CDR-L3 1107368.00126 sequence is SEQ ID NO: 77. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 78. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 79. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 80. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 81. [00135] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 46 and the CDR- L3 sequence is selected from SEQ ID NOS: 77-82. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 77. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 78. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 79. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 80. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 81. [00136] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 47 and the CDR- L3 sequence is selected from SEQ ID NOS: 77-82. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 77. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 78. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 79. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 80. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 81. [00137] In some embodiments, the CDR-H3 sequence is SEQ ID NO: 48 and the CDR- L3 sequence is selected from SEQ ID NOS: 77-82. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 77. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 78. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 79. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 80. In some embodiments, the CDR-L3 sequence is SEQ ID NO: 81. 2.7.1.1.Variants of CDR-H3 – CDR-L3 Pairs [00138] In some embodiments, the CDR-H3 – CDR-L3 pairs provided herein comprise a variant of an illustrative CDR-H3 and/or CDR-L1 sequence provided in this disclosure. [00139] In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-H3 sequence provided in this disclosure. In some embodiments, the CDR-H3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-H3 sequences provided in this disclosure. In some embodiments, the CDR- H3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-H3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some 1107368.00126 embodiments, the amino acid substitutions are conservative amino acid substitutions. [00140] In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a variant of an illustrative CDR-L3 sequence provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of a sequence having at least 70%, 75%, 80%, 85%, 90%, or 95% identity with any of the illustrative CDR-L3 sequences provided in this disclosure. In some embodiments, the CDR-L3 sequence comprises, consists of, or consists essentially of any of the illustrative CDR-L3 sequences provided in this disclosure, with 1, 2, or 3 amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 2.7.2. V_H – V_L Pairs [00141] In some embodiments, the antibody comprises a VH sequence and a VL sequence. [00142] In some embodiments, the VH sequence is a VH sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 89-94 and the VL sequence is a VL sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 101-106. [00143] In some embodiments, the VH sequence is SEQ ID NO: 89 and the VL sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the V_L sequence is SEQ ID NO: 101. In some embodiments, the VL sequence is SEQ ID NO: 102. In some embodiments, the VL sequence is SEQ ID NO: 103. In some embodiments, the VL sequence is SEQ ID NO: 104. In some embodiments, the VL sequence is SEQ ID NO: 105. In some embodiments, the VL sequence is SEQ ID NO: 106. [00144] In some embodiments, the V_H sequence is SEQ ID NO: 90 and the V_L sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the VL sequence is SEQ ID NO: 101. In some embodiments, the VL sequence is SEQ ID NO: 102. In some embodiments, the VL sequence is SEQ ID NO: 103. In some embodiments, the VL sequence is SEQ ID NO: 104. In some embodiments, the VL sequence is SEQ ID NO: 105. In some embodiments, the V_L sequence is SEQ ID NO: 106. [00145] In some embodiments, the VH sequence is SEQ ID NO: 91 and the VL sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the V_L sequence is SEQ ID NO: 101. In some embodiments, the VL sequence is SEQ ID NO: 102. In some embodiments, the VL sequence is SEQ ID NO: 103. In some embodiments, the VL sequence is SEQ ID NO: 104. In some embodiments, the V_L sequence is SEQ ID NO: 105. In some embodiments, the 1107368.00126 VL sequence is SEQ ID NO: 106. [00146] In some embodiments, the VH sequence is SEQ ID NO: 92 and the VL sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the VL sequence is SEQ ID NO: 101. In some embodiments, the VL sequence is SEQ ID NO: 102. In some embodiments, the V_L sequence is SEQ ID NO: 103. In some embodiments, the V_L sequence is SEQ ID NO: 104. In some embodiments, the VL sequence is SEQ ID NO: 105. In some embodiments, the V_L sequence is SEQ ID NO: 106. [00147] In some embodiments, the VH sequence is SEQ ID NO: 93 and the VL sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the VL sequence is SEQ ID NO: 101. In some embodiments, the V_L sequence is SEQ ID NO: 102. In some embodiments, the VL sequence is SEQ ID NO: 103. In some embodiments, the VL sequence is SEQ ID NO: 104. In some embodiments, the V_L sequence is SEQ ID NO: 105. In some embodiments, the VL sequence is SEQ ID NO: 106. [00148] In some embodiments, the VH sequence is SEQ ID NO: 94 and the VL sequence is selected from SEQ ID NOS: 101-106. In some embodiments, the V_L sequence is SEQ ID NO: 101. In some embodiments, the VL sequence is SEQ ID NO: 102. In some embodiments, the V_L sequence is SEQ ID NO: 103. In some embodiments, the V_L sequence is SEQ ID NO: 104. In some embodiments, the VL sequence is SEQ ID NO: 105. In some embodiments, the V_L sequence is SEQ ID NO: 106. 2.7.3. CDR-H1 + CDR-H2 + CDR-H3 + CDR-L1 + CDR-L2 + CDR-L3 [00149] In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 1, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 67, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 2, a Kabat CDR-H2 sequence comprising SEQ ID NO: 24, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 46 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 56, a CDR-L2 sequence comprising SEQ ID NO: 68, and a CDR-L3 sequence SEQ ID NO: 78. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID 1107368.00126 NO: 3, a Kabat CDR-H2 sequence comprising SEQ ID NO: 25, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 47 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 57, a CDR-L2 sequence comprising SEQ ID NO: 69, and a CDR-L3 sequence SEQ ID NO: 79. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 4, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 3, a Kabat CDR-H2 sequence comprising SEQ ID NO: 25, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 48 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 57, a CDR-L2 sequence comprising SEQ ID NO: 69, and a CDR-L3 sequence SEQ ID NO: 79. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 4, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 58, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 80. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 5, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 59, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 81. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Kabat CDR-H1 sequence comprising SEQ ID NO: 4, a Kabat CDR-H2 sequence comprising SEQ ID NO: 23, and a Kabat CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 59, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 81. [00150] In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 12, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 1107368.00126 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 67, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 13, a Chothia CDR-H2 sequence comprising SEQ ID NO: 35, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 46 and a VL sequence comprising a CDR- L1 sequence comprising SEQ ID NO: 56, a CDR-L2 sequence comprising SEQ ID NO: 68, and a CDR-L3 sequence SEQ ID NO: 78. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 36, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 47 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 57, a CDR-L2 sequence comprising SEQ ID NO: 69, and a CDR-L3 sequence SEQ ID NO: 79. [00151] In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 15, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 55, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 77. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 14, a Chothia CDR-H2 sequence comprising SEQ ID NO: 36, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 48 and a VL sequence comprising a CDR- L1 sequence comprising SEQ ID NO: 57, a CDR-L2 sequence comprising SEQ ID NO: 69, and a CDR-L3 sequence SEQ ID NO: 79. [00152] In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 15, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 58, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 80. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a V_H sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 16, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR- 1107368.00126 L1 sequence comprising SEQ ID NO: 59, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 81. In some embodiments, the binding domain capable of binding to an ACKR4 epitope comprises a VH sequence comprising a Chothia CDR-H1 sequence comprising SEQ ID NO: 16, a Chothia CDR-H2 sequence comprising SEQ ID NO: 34, and a Chothia CDR-H3 sequence comprising SEQ ID NO: 45 and a VL sequence comprising a CDR-L1 sequence comprising SEQ ID NO: 59, a CDR-L2 sequence comprising SEQ ID NO: 70, and a CDR-L3 sequence SEQ ID NO: 81. 2.7.3.1.Variants of V_H – V_L Pairs [00153] In some embodiments, the V_H – V_L pairs provided herein comprise a variant of an illustrative VH and/or VL sequence provided in this disclosure. [00154] In some embodiments, the VH sequence comprises, consists of, or consists essentially of a variant of an illustrative V_H sequence provided in this disclosure. In some embodiments, the VH sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.1% identity with any of the illustrative VH sequences provided in this disclosure. [00155] In some embodiments, the VH sequence comprises, consists of, or consists essentially of any of the illustrative V_H sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. [00156] In some embodiments, the V_L sequence comprises, consists of, or consists essentially of a variant of an illustrative VL sequence provided in this disclosure. In some embodiments, the V_L sequence comprises, consists of, or consists essentially of a sequence having at least 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 99.05% identity with any of the illustrative V_L sequences provided in this disclosure. [00157] In some embodiments, the V_L sequence comprises, consists of, or consists essentially of any of the illustrative VL sequences provided in this disclosure, 20 or fewer, 19 or fewer, 18 or fewer, 17 or fewer, 16 or fewer, 15 or fewer, 14 or fewer, 13 or fewer, 12 or fewer, 11 or fewer, 10 or fewer, 9 or fewer, 8 or fewer, 7 or fewer, 6 or fewer, 5 or fewer, 4 or fewer, 3 or fewer, 2 or fewer, or 1 or fewer amino acid substitutions. In some embodiments, the amino acid substitutions are conservative amino acid substitutions. 1107368.00126 2.7.4 HC + LC [00158] In some embodiments, the antibody comprises or consists of one or more heavy chains consisting of an HC sequence and one or more light chains consisting of an LC sequence. In some embodiments, the antibody comprises or consists of two identical heavy chains consisting of an HC sequence and two identical light chains consisting of an LC sequence. [00159] In some embodiments, the HC sequence is an HC sequence comprising, consisting of, or consisting essentially of a sequence selected from SEQ ID NOS: 113-120 and the LC sequence is an LC sequence comprising, consisting of, or consisting essentially of SEQ ID NOS: 128-133. In some embodiments, the HC sequence is an HC sequence consisting of a sequence selected from SEQ ID NOS: 113-120 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-133. [00160] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 113 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-133. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00161] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 114 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00162] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 115 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence 1107368.00126 is SEQ ID NO: 133. [00163] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 116 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00164] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 117 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00165] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 118 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00166] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 119 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00167] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 120 and the LC sequence is an LC sequence consisting of a sequence selected from SEQ ID NOS: 128-134. In some embodiments, the LC sequence is SEQ ID NO: 128. In some 1107368.00126 embodiments, the LC sequence is SEQ ID NO: 129. In some embodiments, the LC sequence is SEQ ID NO: 130. In some embodiments, the LC sequence is SEQ ID NO: 131. In some embodiments, the LC sequence is SEQ ID NO: 132. In some embodiments, the LC sequence is SEQ ID NO: 133. [00168] In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 113 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 128. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 114 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 129. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 115 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 130. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 116 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 131. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 117 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 130. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 118 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 132. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 119 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 133. In some embodiments, the HC sequence is an HC sequence consisting of SEQ ID NO: 124 and the LC sequence is an LC sequence consisting of sequence SEQ ID NO: 133. 2.8. Consensus Sequences [00169] In some embodiments, provided herein are anti-ACKR antibodies comprising one or more sequences defined by consensus sequences. Each consensus sequence is based, at least in part, on one or more alignments of two or more useful anti-ACKR4 CDR sequences provided in this disclosure. Based on such alignments, a person of skill in the art would recognize that different amino acid residues may useful in certain positions of the CDRs. Accordingly, each consensus sequence encompasses two or more useful anti-ACKR4 CDR sequences. 2.8.1. CDR-H3 Consensus Sequences [00170] In some embodiments, the antibody comprises a CDR-H3 sequence defined by the consensus sequence D-I-I-T-H-Y-Y-У8-Y-G-M-D-V (SEQ ID NOS: 47-48), where У8 is Y or T. In some embodiments, У8 is T. In some embodiments, У8 is Y. 1107368.00126 2.8.2. Chothia CDR-H2 Consensus Sequences [00171] In some embodiments, the antibody comprises a Chothia CDR-H2 sequence defined by the consensus sequence ε1-ε2- ε3-G- ε5-ε6 (SEQ ID NOS: 34-35), where ε1 is S or W; ε₂ is G or Y; ε₃ is G or D; ε₅ is G or S; and ε₆ is S or N. [00172] In some embodiments, when ε₁ is S; ε₂ is G; ε₃ is G; ε₅ is G; and ε₆ is S. In some embodiments, when ε1 is W; ε2 is Y; ε3 is D; ε5 is S; and ε6 is N. 2.8.3. Chothia CDR-H1 Consensus Sequences [00173] In some embodiments, the antibody comprises a Chothia CDR-H1 sequence defined by the consensus sequence G-F-T-F-S- Ω6-Ω7 (SEQ ID NOS: 12-13 and 15-16), where Ω₆ is T, S or Y and Ω₇ is C, Y, or S. [00174] In some embodiments, when Ω6 is T; Ω7 is C, or S. [00175] In some embodiments, when Ω7 is S; Ω6 is T or Y. [00176] In some embodiments, when Ω6 is S; Ω7 is Y. In some embodiments, when Ω6 is Y; Ω₇ is S. In some embodiments, when Ω₆ is T; Ω₇ is C. In some embodiments, when Ω₆ is T; Ω7 is S. 2.8.4. Kabat CDR-H2 Consensus Sequences [00177] In some embodiments, the antibody comprises a Kabat CDR-H2 sequence defined by the consensus sequence β1-I-β3-β4-β5-G-β7-β8-β9-Y-Y-A-D-S-V-K-G (SEQ ID NOS: 23-24) where β₁ is A or V; β₃ is S or W; β₄ is G or Y; β₅ is G or D; β₇ is S or G; β₈ is N or S; and β9 is T or K. [00178] In some embodiments, when β1 is A; β3 is S; β4 is G; β5 is G; β7 is G; β8 is S; and β₉ is T. In some embodiments, when β₁ is V; β₃ is W; β₄ is Y; β₅ is D; β₇ is S; β₈ is N; and β9 is K. 2.8.5. Kabat CDR-H1 Consensus Sequences [00179] In some embodiments, the antibody comprises a Kabat CDR-H1 sequence defined by the consensus sequence Δ1-Δ2-A-M-S (SEQ ID NOS: 1 and 4-5), where Δ1 is T or Y; and Δ₂ is C or S. [00180] In some embodiments, when Δ1 is T; Δ2 is C or S. In some embodiments, when Δ2 is S; Δ1 is T or Y. [00181] In some embodiments, when Δ₁ is T; Δ₂ is C. In some embodiments, when Δ₁ is T; Δ2 is S. In some embodiments, when Δ1 is Y; Δ1 is S. 1107368.00126 2.8.6. CDR-L3 Consensus Sequences [00182] In some embodiments, the antibody comprises a CDR-L3 sequence defined by the consensus sequence π1- Q-π3-π4- π5-W-P- π8-T (SEQ ID NOS: 77-78 and 80-81), where π1 is Q or M; π₃ is R or G; π₄ is T, S, or A; π₅.is N, H, or R; and π₈ is P or F. [00183] In some embodiments, when π₁ is Q; π₃ is R; π₄ is S or A; π₅.is N or R; and π₈ is P. In some embodiments, when π4 is S; π1 is Q; π3 is R; π5.is N or R; and π8 is P. In some embodiments, when π₅ is R; π₁ is Q; π₃ is R; π₄.is S or A; and π₈ is P. [00184] In some embodiments, when π1 is Q; π3 is R; π4 is S; π5.is N; and π8 is P. In some embodiments, when π1 is M; π3 is G; π4 is T; π5.is H; and π8 is F. In some embodiments, when π₁ is Q; π₃ is R; π₄ is S; π₅.is R; and π₈ is P. In some embodiments, when π₁ is Q; π₃ is R; π4 is A; π5.is R; and π8 is P. 2.8.7. CDR-L2 Consensus Sequences [00185] In some embodiments, the antibody comprises a CDR-L2 sequence defined by the consensus sequence ψ1- ψ2- ψ3-N-R- ψ6-ψ7 (SEQ ID NOS: 67-70), where ψ1 is D, R, or A; ψ₂ is V or A; ψ₃ is N or S; ψ₆ is A, D or P; and ψ₇ is T or S. [00186] In some embodiments, when ψ1 is D; ψ2 is A or V; ψ3 is S; ψ6 is A; and ψ7 is T. In some embodiments, when ψ₇ is S; ψ₁ is R or A; ψ₂ is V; ψ₃ is S or N; ψ₆ is D or P. In some embodiments, when ψ2 is V; ψ1 is R, A, or D; ψ3 is S or N; ψ6 is D, P, or A; and ψ7 is S or T. In some embodiments, when ψ3 is S; ψ1 is R or D; ψ2 is A or V; ψ6 is D or A; and ψ7 is S or T. [00187] In some embodiments, when ψ₁ is D; ψ₂ is A; ψ₃ is S; ψ₆ is A; and ψ₇ is T. In some embodiments, when ψ1 is R; ψ2 is V; ψ3 is S; ψ6 is D; and ψ7 is S. In some embodiments, when ψ₁ is A; ψ₂ is V; ψ₃ is N; ψ₆ is P; and ψ₇ is S. In some embodiments, when ψ₁ is D; ψ₂ is V; ψ3 is S; ψ6 is A; and ψ7 is T. 2.8.8. CDR-L1 Consensus Sequences [00188] In some embodiments, the antibody comprises a CDR-L1 sequence defined by the consensus sequence R-A-A-Q-S-V-ϕ7-ϕ8-S-L-A (SEQ ID NOS: 55 and 58-59), where ϕ7 is S or R; and ϕ₈ is S or R. [00189] In some embodiments, when ϕ₇ is S; ϕ₈ is S or R. In some embodiments, when ϕ8 is R; ϕ7 is S or R. [00190] In some embodiments, when ϕ7 is S; ϕ8 is R. In some embodiments, when ϕ7 is S; ϕ₈ is S. In some embodiments, when ϕ₇ is R; ϕ₈ is R. 1107368.00126 3. Inhibition of ACKR4 [00191] In some embodiments, the antibody decreases the affinity of ACKR4 for its chemokines. In some embodiments, the antibody disrupts the association of ACKR4 with CCL19, CCL21, CCL25, and/or other C-C type chemokines. In some embodiments the antibody prevents ACKR4 internalization of chemokines. In some embodimentsthe antibody prevents ACKR4 degradation of chemokines. In some embodiments the antibody inhibits chemokine scavenging by ACKR4. [00192] In some embodiments, the antibody increases internalization of ACKR4. In some embodiments, the antibody down-regulates ACKR4. [00193] In some embodiments, the decrease is about or less than a 10% decrease, about or less than a 20% decrease, about or less than a 30% decrease, about or less than a 40% decrease, about or less than a 50% decrease, about or less than a 60% decrease, about or less than a 70% decrease, about or less than an 80% decrease, about or less than a 90% decrease, or about a complete decrease. In some embodiments, the increase is about or greater than a 10% increase, about or greater than a 20% increase, about or greater than a 30% increase, about or greater than a 40% increase, about or greater than a 50% increase, about or greater than a 60% increase, about or greater than a 70% increase, about or greater than an 80% increase, about or greater than a 90% increase, or a complete increase. 4. ACKR4 Assays [00194] In some embodiments, the antibody binds to an epitope of ACKR4. An epitope often consists of a number of contiguous amino acids such as, for example, without limitation, 5-6 amino acids. In some embodiments, the epitope comprises or consists of contiguous or non-contiguous amino acids. In some embodiments, the contiguous or non-contiguous amino acids are within a domain of ACKR4. [00195] In some embodiments, ACKR4 has a sequence identical to the amino acid sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope has an amino acid sequence that is within the amino acid sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope has an amino acid sequence that is 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identical to a sequence that is within the sequence set forth in SEQ ID NO: 147. [00196] In some embodiments, the epitope has a sequence that has a 60%, 65%, 70%, 75%, 80%, 85%, 90%, or 95% identity to a sequence that is within the sequence set forth in SEQ ID NO: 147. In some embodiments, the epitope has 1, 2, 3, 4, 5, 6, 7, 8, or 9 substitutions 1107368.00126 from a sequence that is within the sequence set forth in forth in SEQ ID NO: 147. In some embodiments, the epitope has 1, 2 or 3 substitutions from residues a sequence that is within the sequence set forth in SEQ ID NO: 147. [00197] In some embodiments, the antibody competes with any of the antibodies set forth herein. Competition could be, for example, without limitation, binding competition, inhibition competition, or any other form of competition. 5. Glycosylation Variants [00198] In some embodiments, an antibody may be altered to increase, decrease or eliminate the extent to which it is glycosylated. Glycosylation of polypeptides is typically either “N-linked” or “O-linked.” [00199] “N-linked” glycosylation refers to the attachment of a carbohydrate moiety to the side chain of an asparagine residue. The tripeptide sequences asparagine-X-serine and asparagine-X-threonine, where X is any amino acid except proline, are the recognition sequences for enzymatic attachment of the carbohydrate moiety to the asparagine side chain. Thus, the presence of either of these tripeptide sequences in a polypeptide creates a potential glycosylation site. [00200] “O-linked” glycosylation refers to the attachment of one of the sugars N- acetylgalactosamine, galactose, or xylose to a hydroxyamino acid, most commonly serine or threonine, although 5-hydroxyproline or 5-hydroxylysine may also be used. [00201] Addition or deletion of N-linked glycosylation sites to the antibody may be accomplished by altering the amino acid sequence such that one or more of the above-described tripeptide sequences is created or removed. Addition or deletion of O-linked glycosylation sites may be accomplished by addition, deletion, or substitution of one or more serine or threonine residues in or to (as the case may be) the sequence of an antibody. [00202] In certain embodiments, the antibody is glycosylated. In certain embodiments, the antibody is deglycosylated. Carbohydrates may be removed by standard techniques. In certain embodiments, the antibody is aglycosylated, for instance by expression in a system that does not glycosylate. 6. Fc Variants [00203] In some embodiments, amino acid modifications may be introduced into the Fc region of an antibody provided herein to generate an Fc region variant. In some embodiments, the Fc region variant possesses some, but not all, effector functions. Such antibodies may be 1107368.00126 useful, for example, in applications in which the half-life of the antibody in vivo is important, yet certain effector functions are unnecessary or deleterious. Examples of effector functions include complement-dependent cytotoxicity (CDC) and antibody-directed complement- mediated cytotoxicity (ADCC). Numerous substitutions or substitutions or deletions with altered effector function are known in the art. [00204] In some embodiments, the Fc is modified. In some embodiments, a hinge of an IgG1 or IgG4 antibody is modified. Modification of a hinge region stabilizes an antibody and prevents formation of unwanted bispecific antibodies. In some embodiments, an IgG Fc is engineered to modulate antibody effector function (See Wang et al., Protein Cell, 2018, Jan; 9(1): 63–73), which is incorporated by reference herein in its entirety, including any drawings). [00205] Non-limiting examples of in vitro assays to assess ADCC activity of a molecule of interest are provided in U.S. Patent Nos. 5,500,362 and 5,821,337; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1986, 83:7059-7063; Hellstrom et al., Proc. Natl. Acad. Sci. U.S.A., 1985, 82:1499-1502; and Bruggemann et al., J. Exp. Med., 1987, 166:1351-1361. Useful effector cells for such assays include peripheral blood mononuclear cells (PBMC) and Natural Killer (NK) cells. Alternatively, or additionally, ADCC activity of the molecule of interest may be assessed in vivo, using an animal model such as that disclosed in Clynes et al. Proc. Natl. Acad. Sci. U.S.A., 1998, 95:652-656. [00206] C1q binding assays may also be carried out to confirm that the antibody is unable to bind C1q and hence lacks CDC activity. Examples of C1q binding assays include those described in WO 2006/029879 and WO 2005/100402. [00207] Complement activation assays include those described, for example, in Gazzano-Santoro et al., J. Immunol. Methods, 1996, 202:163-171; Cragg et al., Blood, 2003, 101:1045-1052; and Cragg and Glennie, Blood, 2004, 103:2738-2743. [00208] FcRn binding and in vivo clearance (half-life determination) can also be measured, for example, using the methods described in Petkova et al., Intl. Immunol., 2006, 18:1759-1769. 7. Preparation of Antibodies 7.1. Antigen Preparation [00209] The ACKR4 antigen to be used for production of antibodies may be intact ACKR4 or a fragment of ACKR4. The intact ACKR4, or fragment of ACKR4, may be in the form of an isolated protein or expressed by a cell. Other forms of ACKR4 useful for generating 1107368.00126 antibodies will be apparent to those skilled in the art. 7.2. Monoclonal Antibodies [00210] Monoclonal antibodies may be obtained, for example, using the hybridoma method first described by Kohler et al., Nature, 1975, 256:495-497, and/or by recombinant DNA methods (see e.g., U.S. Patent No. 4,816,567). Monoclonal antibodies may also be obtained, for example, using phage or yeast-based libraries. See e.g., U.S. Patent Nos. 8,258,082 and 8,691,730. [00211] In the hybridoma method, a mouse or other appropriate host animal is immunized to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the protein used for immunization. Alternatively, lymphocytes may be immunized in vitro. Lymphocytes are then fused with myeloma cells using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell. See Goding J.W., Monoclonal Antibodies: Principles and Practice 3^rd ed. (1986) Academic Press, San Diego, CA. [00212] The hybridoma cells are seeded and grown in a suitable culture medium that contains one or more substances that inhibit the growth or survival of the unfused, parental myeloma cells. For example, if the parental myeloma cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (HAT medium), which substances prevent the growth of HGPRT-deficient cells. [00213] Useful myeloma cells are those that fuse efficiently, support stable high-level production of antibody by the selected antibody-producing cells, and are sensitive media conditions, such as the presence or absence of HAT medium. Among these, preferred myeloma cell lines are murine myeloma lines, such as those derived from MOP-21 and MC-11 mouse tumors (available from the Salk Institute Cell Distribution Center, San Diego, CA), and SP-2 or X63-Ag8-653 cells (available from the American Type Culture Collection, Rockville, MD). Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. See e.g., Kozbor, J. Immunol., 1984, 133:3001. [00214] After the identification of hybridoma cells that produce antibodies of the desired specificity, affinity, and/or biological activity, selected clones may be subcloned by limiting dilution procedures and grown by standard methods. See Goding, supra. Suitable culture media for this purpose include, for example, D-MEM or RPMI-1640 medium. In addition, the hybridoma cells may be grown in vivo as ascites tumors in an animal. 1107368.00126 [00215] DNA encoding the monoclonal antibodies may be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of the monoclonal antibodies). Thus, the hybridoma cells can serve as a useful source of DNA encoding antibodies with the desired properties. Once isolated, the DNA may be placed into expression vectors, which are then transfected into host cells such as bacteria (e.g., E. coli), yeast (e.g., Saccharomyces or Pichia sp.), COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce antibody, to produce the monoclonal antibodies. 7.3. Humanized Antibodies [00216] Humanized antibodies may be generated by replacing most, or all, of the structural portions of a monoclonal antibody with corresponding human antibody sequences. Consequently, a hybrid molecule is generated in which only the antigen-specific variable, or CDR, is composed of non-human sequence. Methods to obtain humanized antibodies include those described in, for example, Winter and Milstein, Nature, 1991, 349:293-299; Rader et al., Proc. Nat. Acad. Sci. U.S.A., 1998, 95:8910-8915; Steinberger et al., J. Biol. Chem., 2000, 275:36073-36078; Queen et al., Proc. Natl. Acad. Sci. U.S.A., 1989, 86:10029-10033; and U.S. Patent Nos.5,585,089, 5,693,761, 5,693,762, and 6,180,370. 7.4. Human Antibodies [00217] Human antibodies can be generated by a variety of techniques known in the art, for example by using transgenic animals (e.g., humanized mice). See, e.g., Jakobovits et al., Proc. Natl. Acad. Sci. U.S.A., 1993, 90:2551; Jakobovits et al., Nature, 1993, 362:255-258; Bruggermann et al., Year in Immuno., 1993, 7:33; and U.S. Patent Nos. 5,591,669, 5,589,369 and 5,545,807. Human antibodies can also be derived from phage-display libraries (see e.g., Hoogenboom et al., J. Mol. Biol., 1991, 227:381-388; Marks et al., J. Mol. Biol., 1991, 222:581-597; and U.S. Pat. Nos. 5,565,332 and 5,573,905). Human antibodies may also be generated by in vitro activated B cells (see e.g., U.S. Patent. Nos. 5,567,610 and 5,229,275). Human antibodies may also be derived from yeast-based libraries (see e.g., U.S. Patent No. 8,691,730). 8. Vectors, Host Cells, and Recombinant Methods [00218] A second aspect provides isolated nucleic acids encoding anti-ACKR4 antibodies, vectors, and host cells comprising the nucleic acids and recombinant techniques for the production of the antibodies. 1107368.00126 [00219] For recombinant production of the antibody, the nucleic acid encoding it may be isolated and inserted into a replicable vector for further cloning (i.e., amplification of the DNA) or expression. In some embodiments, the nucleic acid may be produced by homologous recombination, for example as described in U.S. Patent No.5,204,244. [00220] Many different vectors are known in the art. The vector components generally include, but are not limited to, one or more of the following: a signal sequence, an origin of replication, one or more marker genes, an enhancer element, a promoter, and a transcription termination sequence, for example as described in U.S. Patent No.5,534,615. [00221] Suitable host cells include any prokaryotic (e.g., bacterial), lower eukaryotic (e.g., yeast), or higher eukaryotic (e.g., mammalian) cells. Suitable prokaryotes include eubacteria, such as Gram-negative or Gram-positive organisms, for example, Enterobacteriaceae such as Escherichia (E. coli), Enterobacter, Erwinia, Klebsiella, Proteus, Salmonella (S. typhimurium), Serratia (S. marcescans), Shigella, Bacilli (B. subtilis and B. licheniformis), Pseudomonas (P. aeruginosa), and Streptomyces. One useful E. coli cloning host is E. coli 294, although other strains such as E. coli B, E. coli X1776, and E. coli W3110 are suitable. [00222] In addition to prokaryotes, eukaryotic microbes such as filamentous fungi or yeast are also suitable cloning or expression hosts for anti-ACKR4 antibody-encoding vectors. Saccharomyces cerevisiae, or common baker's yeast, is a commonly used lower eukaryotic host microorganism. However, a number of other genera, species, and strains are available and useful, such as Schizosaccharomyces pombe, Kluyveromyces (K. lactis, K. fragilis, K. bulgaricus K. wickeramii, K. waltii, K. drosophilarum, K. thermotolerans, and K. marxianus), Yarrowia, Pichia pastoris, Candida (C. albicans), Trichoderma reesia, Neurospora crassa, Schwanniomyces (S. occidentalis), and filamentous fungi such as, for example Penicillium, Tolypocladium, and Aspergillus (A. nidulans and A. niger). [00223] Useful mammalian host cells include COS-7 cells, HEK293 cells; baby hamster kidney (BHK) cells; Chinese hamster ovary (CHO); mouse sertoli cells; African green monkey kidney cells (VERO-76), and the like. [00224] The host cells used to produce the anti-ACKR4 antibody of this invention may be cultured in a variety of media. Commercially available media such as, for example, Ham's F10, Minimal Essential Medium (MEM), RPMI-1640, and Dulbecco's Modified Eagle's Medium (DMEM) are suitable for culturing the host cells. In addition, any of the media 1107368.00126 described in Ham et al., Meth. Enz., 1979, 58:44; Barnes et al., Anal. Biochem., 1980, 102:255; and U.S. Patent Nos. 4,767,704, 4,657,866, 4,927,762, 4,560,655, and 5,122,469, or WO 90/03430 and WO 87/00195 may be used. [00225] Any of these media may be supplemented as necessary with hormones and/or other growth factors (such as insulin, transferrin, or epidermal growth factor), salts (such as sodium chloride, calcium, magnesium, and phosphate), buffers (such as HEPES), nucleotides (such as adenosine and thymidine), antibiotics, trace elements (defined as inorganic compounds usually present at final concentrations in the micromolar range), and glucose or an equivalent energy source. Any other necessary supplements may also be included at appropriate concentrations that would be known to those skilled in the art. [00226] The culture conditions, such as temperature, pH, and the like, are those previously used with the host cell selected for expression, and will be apparent to the ordinarily skilled artisan. [00227] When using recombinant techniques, the antibody can be produced intracellularly, in the periplasmic space, or directly secreted into the medium. If the antibody is produced intracellularly, as a first step, the particulate debris, either host cells or lysed fragments, is removed, for example, by centrifugation or ultrafiltration. For example, Carter et al. (Bio/Technology, 1992, 10:163-167) describes a procedure for isolating antibodies which are secreted to the periplasmic space of E. coli. Briefly, cell paste is thawed in the presence of sodium acetate (pH 3.5), EDTA, and phenylmethylsulfonylfluoride (PMSF) over about 30 minutes. Cell debris can be removed by centrifugation. [00228] In some embodiments, the antibody is produced in a cell-free system. In some embodiments, the cell-free system is an in vitro transcription and translation system as described in Yin et al., mAbs, 2012, 4:217-225, incorporated by reference in its entirety. In some embodiments, the cell-free system utilizes a cell-free extract from a eukaryotic cell or from a prokaryotic cell. In some embodiments, the prokaryotic cell is E. coli. Cell-free expression of the antibody may be useful, for example, where the antibody accumulates in a cell as an insoluble aggregate, or where yields from periplasmic expression are low. [00229] Where the antibody is secreted into the medium, supernatants from such expression systems are generally first concentrated using a commercially available protein concentration filter, for example, an Amicon^® or Millipore^® Pellcon^® ultrafiltration unit. A protease inhibitor such as PMSF may be included in any of the foregoing steps to inhibit 1107368.00126 proteolysis and antibiotics may be included to prevent the growth of adventitious contaminants. [00230] The antibody composition prepared from the cells can be purified using, for example, hydroxylapatite chromatography, gel electrophoresis, dialysis, and affinity chromatography, with affinity chromatography being a particularly useful purification technique. The suitability of protein A as an affinity ligand depends on the species and isotype of any immunoglobulin Fc domain that is present in the antibody. Protein A can be used to purify antibodies that are based on human γ1, γ2, or γ4 heavy chains (Lindmark et al., J. Immunol. Meth., 1983, 62:1-13). Protein G is useful for all mouse isotypes and for human γ3 (Guss et al., EMBO J., 1986, 5:1567-1575). [00231] The matrix to which the affinity ligand is attached is most often agarose, but other matrices are available. Mechanically stable matrices such as controlled pore glass or poly(styrenedivinyl)benzene allow for faster flow rates and shorter processing times than can be achieved with agarose. Where the antibody comprises a CH3 domain, the BakerBond ABX^® resin is useful for purification. [00232] Other techniques for protein purification, such as fractionation on an ion- exchange column, ethanol precipitation, Reverse Phase HPLC, chromatography on silica, chromatography on heparin Sepharose^®, chromatofocusing, SDS-PAGE, and ammonium sulfate precipitation are also available, and can be applied by one of skill in the art. [00233] Following any preliminary purification step(s), the mixture comprising the antibody of interest and contaminants may be subjected to low pH hydrophobic interaction chromatography using an elution buffer at a pH between about 2.5 to about 4.5, generally performed at low salt concentrations (e.g., from about 0 to about 0.25 M salt). 9. Pharmaceutical Compositions and Methods of Administration [00234] A third aspect provides a pharmaceutical composition comprising one or more of the antibodies set forth herein. Any of the antibodies provided herein can be provided in any appropriate pharmaceutical composition and be administered by any suitable route of administration. Suitable routes of administration include, but are not limited to, the inhalation, intra-arterial, intradermal, intramuscular, intraperitoneal, intravenous, nasal, parenteral, pulmonary, and subcutaneous routes. [00235] The pharmaceutical composition may comprise one or more pharmaceutical excipients. Any suitable pharmaceutical excipient may be used, and one of ordinary skill in the art is capable of selecting suitable pharmaceutical excipients. Accordingly, the 1107368.00126 pharmaceutical excipients provided below are intended to be illustrative, and not limiting. Additional pharmaceutical excipients include, for example, those described in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), incorporated by reference in its entirety. [00236] In some embodiments, the pharmaceutical composition comprises an anti- foaming agent. Any suitable anti-foaming agent may be used. In some embodiments, the anti- foaming agent is selected from an alcohol, an ether, an oil, a wax, a silicone, a surfactant, and combinations thereof. In some embodiments, the anti-foaming agent is selected from a mineral oil, a vegetable oil, ethylene bis stearamide, a paraffin wax, an ester wax, a fatty alcohol wax, a long chain fatty alcohol, a fatty acid soap, a fatty acid ester, a silicon glycol, a fluorosilicone, a polyethylene glycol-polypropylene glycol copolymer, polydimethylsiloxane-silicon dioxide, ether, octyl alcohol, capryl alcohol, sorbitan trioleate, ethyl alcohol, 2-ethyl-hexanol, dimethicone, oleyl alcohol, simethicone, and combinations thereof. [00237] In some embodiments, the pharmaceutical composition comprises a cosolvent. Illustrative examples of cosolvents include ethanol, poly(ethylene) glycol, butylene glycol, dimethylacetamide, glycerin, and propylene glycol. [00238] In some embodiments, the pharmaceutical composition comprises a buffer. Illustrative examples of buffers include acetate, borate, carbonate, lactate, malate, phosphate, citrate, hydroxide, diethanolamine, monoethanolamine, glycine, methionine, guar gum, and monosodium glutamate. [00239] In some embodiments, the pharmaceutical composition comprises a carrier or filler. Illustrative examples of carriers or fillers include lactose, maltodextrin, mannitol, sorbitol, chitosan, stearic acid, xanthan gum, and guar gum. [00240] In some embodiments, the pharmaceutical composition comprises a surfactant. Illustrative examples of surfactants include d-alpha tocopherol, benzalkonium chloride, benzethonium chloride, cetrimide, cetylpyridinium chloride, docusate sodium, glyceryl behenate, glyceryl monooleate, lauric acid, macrogol 15 hydroxystearate, myristyl alcohol, phospholipids, polyoxyethylene alkyl ethers, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sodium lauryl sulfate, sorbitan esters, and vitamin E polyethylene(glycol) succinate. [00241] In some embodiments, the pharmaceutical composition comprises an anti- caking agent. Illustrative examples of anti-caking agents include calcium phosphate (tribasic), 1107368.00126 hydroxymethyl cellulose, hydroxypropyl cellulose, and magnesium oxide. [00242] Other excipients that may be used with the pharmaceutical compositions include, for example, albumin, antioxidants, antibacterial agents, antifungal agents, bioabsorbable polymers, chelating agents, controlled release agents, diluents, dispersing agents, dissolution enhancers, emulsifying agents, gelling agents, ointment bases, penetration enhancers, preservatives, solubilizing agents, solvents, stabilizing agents, and sugars. Specific examples of each of these agents are described, for example, in the Handbook of Pharmaceutical Excipients, Rowe et al. (Eds.) 6th Ed. (2009), The Pharmaceutical Press, incorporated by reference in its entirety. [00243] In some embodiments, the pharmaceutical composition comprises a solvent. In some embodiments, the solvent is saline solution, such as a sterile isotonic saline solution or dextrose solution. In some embodiments, the solvent is water for injection. [00244] In some embodiments, the pharmaceutical compositions are in a particulate form, such as a microparticle or a nanoparticle. Microparticles and nanoparticles may be formed from any suitable material, such as a polymer or a lipid. In some embodiments, the microparticles or nanoparticles are micelles, liposomes, or polymersomes. In certain embodiments, a composition provided herein is a pharmaceutical composition or a single unit dosage form. Pharmaceutical compositions and single unit dosage forms provided herein comprise a prophylactically or therapeutically effective amount of one or more prophylactic or therapeutic antibodies. [00245] Further encompassed herein are anhydrous pharmaceutical compositions and dosage forms comprising an antibody, since water can facilitate the degradation of some antibodies. [00246] Anhydrous pharmaceutical compositions and dosage forms provided herein can be prepared using anhydrous or low moisture containing ingredients and low moisture or low humidity conditions. Pharmaceutical compositions and dosage forms that comprise lactose and at least one active ingredient that comprises a primary or secondary amine can be anhydrous if substantial contact with moisture and/or humidity during manufacturing, packaging, and/or storage is expected. [00247] An anhydrous pharmaceutical composition should be prepared and stored such that its anhydrous nature is maintained. Accordingly, anhydrous compositions can be packaged using materials known to prevent exposure to water such that they can be included in suitable 1107368.00126 formulary kits. Examples of suitable packaging include, but are not limited to, hermetically sealed foils, plastics, unit dose containers (e.g., vials), blister packs, and strip packs. [00248] In some embodiments, the pharmaceutical composition further comprises one or both of an antibody to an immune inhibitory receptor or ligand and/or an antibody to an immune stimulatory receptor and/or ligand. In some embodiments, the pharmaceutical composition further comprises an effective amount of at least one of the following: an anti- ILT2 antibody; an anti-ILT-4 antibody; an anti-ILT4 antibody; an anti-KIR2DL4 antibody; an anti-HLA-E antibody; an anti-NKG2A antibody; an anti-HLA-F antibody; an anti-PD-L1 antibody; an anti-PD-1 antibody; an anti-CTLA4 antibody; an anti-CD38 antibody; an anti- CD73 antibody; an anti-A2A receptor antibody; an anti-A2B receptor antibody; an anti- A2A/A2B dual receptor antibody or a combination thereof; an anti-CD39 antibody; an anti- CD73 antibody; an anti-CD47 antibody; and/or a small molecule inhibitor. In some embodiments, the pharmaceutical composition further comprises an anti-Tim-3 antibody; an anti-TIGIT antibody; an anti-VISTAantibody; an anti-CD94 antibody; an anti-ILT2 antibody, an anti-ILT4 antibody, an anti-PD-L1 antibody, and/or an anti-CD47 antibody; a small molecule inhibitor; a bi-specific T cell engager, CAR-T therapy, CAR-NK therapy, CAR- Macrophage therapy, engineered cell therapy, and/or adaptive T cell therapy; an oncolytic virus; a chemotherapy; and/or an ADCC capable therapy using effector competent antibodies such as anti-CTLA4, anti-CD19, anti-CD20, anti-EGFR, anti-Her2, anti- SLAMF7, anti-CD52, anti-BCMA, anti-GD2, anti-CD38, and/or anti-CCR4. In some embodiments, ADCC capable therapy is enhanced ADCC capable therapy. In some embodiments, the effector is enhanced through afucosylation, point mutations, or another method. 9.1. Parenteral Dosage Forms [00249] In some embodiments parenteral dosage forms are provided. Parenteral dosage forms can be administered to subjects by various routes including, but not limited to, subcutaneous, intravenous (including bolus injection), intramuscular, and intra-arterial. Because their administration typically bypasses subjects’ natural defenses against contaminants, parenteral dosage forms are typically, sterile or capable of being sterilized prior to administration to a subject. Examples of parenteral dosage forms include, but are not limited to, solutions ready for injection, dry products ready to be dissolved or suspended in a pharmaceutically acceptable vehicle for injection, suspensions ready for injection, and emulsions. 1107368.00126 [00250] Suitable vehicles that can be used to provide parenteral dosage forms are well known to those skilled in the art. Examples include, but are not limited to: Water for Injection USP; aqueous vehicles such as, but not limited to, Sodium Chloride Injection, Ringer’s Injection, Dextrose Injection, Dextrose and Sodium Chloride Injection, and Lactated Ringer’s Injection; water miscible vehicles such as, but not limited to, ethyl alcohol, polyethylene glycol, and polypropylene glycol; and non-aqueous vehicles such as, but not limited to, corn oil, cottonseed oil, peanut oil, sesame oil, ethyl oleate, isopropyl myristate, and benzyl benzoate. [00251] Excipients that increase the solubility of one or more of the antibodies disclosed herein can also be incorporated into the parenteral dosage forms. 9.2. Dosage and Unit Dosage Forms [00252] In human therapeutics, the doctor will determine the dosology which she considers most appropriate according to a preventive or curative treatment and according to the age, weight, condition and other factors specific to the subject to be treated. [00253] The amount of the antibody or composition which will be effective in the prevention or treatment of a disorder or one or more symptoms thereof will vary with the nature and severity of the disease or condition, and the route by which the antibody is administered. The frequency and dosage will also vary according to factors specific for each subject depending on the specific therapy (e.g., therapeutic or prophylactic agents) administered, the severity of the disorder, disease, or condition, the route of administration, as well as age, body, weight, response, and the past medical history of the subject. Effective doses may be extrapolated from dose-response curves derived from in vitro or animal model test systems. [00254] In certain embodiments, exemplary doses of a composition include milligram or microgram amounts of the antibody per kilogram of subject or sample weight (e.g., about 10 micrograms per kilogram to about 50 milligrams per kilogram, about 100 micrograms per kilogram to about 25 milligrams per kilogram, or about 100 microgram per kilogram to about 10 milligrams per kilogram). In some embodiments, the dosage of the antibody provided herein, based on weight of the antibody, administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg/kg, 1 mg/kg, 2 mg/kg, 3 mg/kg, 4 mg/kg, 5 mg/kg, 6 mg/kg, 10 mg/kg, or 15 mg/kg or more of a subject’s body weight. In some embodiments, the dosage of the composition or a composition provided herein administered to prevent, treat, manage, or ameliorate a disorder, or one or more symptoms thereof in a subject is 0.1 mg to 200 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1107368.00126 0.1 mg to 20 mg, 0.1 mg to 15 mg, 0.1 mg to 10 mg, 0.1 mg to 7.5 mg, 0.1 mg to 5 mg, 0.1 to 2.5 mg, 0.25 mg to 20 mg, 0.25 to 15 mg, 0.25 to 12 mg, 0.25 to 10 mg, 0.25 mg to 7.5 mg, 0.25 mg to 5 mg, 0.25 mg to 2.5 mg, 0.5 mg to 20 mg, 0.5 to 15 mg, 0.5 to 12 mg, 0.5 to 10 mg, 0.5 mg to 7.5 mg, 0.5 mg to 5 mg, 0.5 mg to 2.5 mg, 1 mg to 20 mg, 1 mg to 15 mg, 1 mg to 12 mg, 1 mg to 10 mg, 1 mg to 7.5 mg, 1 mg to 5 mg, or 1 mg to 2.5 mg. [00255] The dose can be administered according to a suitable schedule, for example, once, two times, three times, or for times weekly. It may be necessary to use dosages of the antibody outside the ranges disclosed herein in some cases, as will be apparent to those of ordinary skill in the art. Furthermore, it is noted that the clinician or treating physician will know how and when to interrupt, adjust, or terminate therapy in conjunction with subject response. [00256] Different therapeutically effective amounts may be applicable for different diseases and conditions, as will be readily known by those of ordinary skill in the art. Similarly, amounts sufficient to prevent, manage, treat or ameliorate such disorders, but insufficient to cause, or sufficient to reduce, adverse effects associated with the antibodies provided herein are also encompassed by the herein described dosage amounts and dose frequency schedules. Further, when a subject is administered multiple dosages of a composition provided herein, not all of the dosages need be the same. For example, the dosage administered to the subject may be increased to improve the prophylactic or therapeutic effect of the composition or it may be decreased to reduce one or more side effects that a particular subject is experiencing. [00257] In some embodiments, treatment or prevention can be initiated with one or more loading doses of an antibody or composition provided herein followed by one or more maintenance doses. [00258] In some embodiments, a dose of an antibody or composition provided herein can be administered to achieve a steady-state concentration of the antibody in blood or serum of the subject. The steady-state concentration can be determined by measurement according to techniques available to those of skill or can be based on the physical characteristics of the subject such as height, weight and age. [00259] In some embodiments, administration of the same composition may be repeated and the administrations may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months. In some embodiments, administration of the same prophylactic or therapeutic agent may be repeated and the 1107368.00126 administration may be separated by at least 1 day, 2 days, 3 days, 5 days, 10 days, 15 days, 30 days, 45 days, 2 months, 75 days, 3 months, or 6 months. 10. Therapeutic Applications [00260] A fourth aspect provides a method of treating an individual having a disease or condition comprising administering any of the antibodies set forth herein to an individual in need thereof. For therapeutic applications, the antibodies of the invention are administered to a mammal, generally a human, in a pharmaceutically acceptable dosage form such as those known in the art and those discussed above. Alternatively, the antibodies of the invention may be administered to a human intravenously as a bolus or by continuous infusion over a period of time, by intramuscular, intraperitoneal, intra-cerebrospinal, subcutaneous, intra-articular, intrasynovial, intrathecal, or intratumoral routes. The antibodies also are suitably administered by peritumoral, intralesional, or perilesional routes, to exert local as well as systemic therapeutic effects. The intraperitoneal route may be particularly useful, for example, in the treatment of ovarian tumors. [00261] The antibodies provided herein may be useful for the treatment of any disease or condition, such as cancer, autoimmune disease, and infection. [00262] Any suitable cancer may be treated with the antibodies provided herein. Illustrative suitable cancers include, for example, acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), adrenocortical carcinoma, anal cancer, appendix cancer, astrocytoma, basal cell carcinoma, brain tumor, bile duct cancer, bladder cancer, bone cancer, breast cancer, bronchial tumor, Burkitt Lymphoma, carcinoma of unknown primary origin, cardiac tumor, cervical cancer, chordoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myeloproliferative neoplasm, colon cancer, colorectal cancer, craniopharyngioma, cutaneous T-cell lymphoma, ductal carcinoma, embryonal tumor, endometrial cancer, ependymoma, esophageal cancer, esthesioneuroblastoma, fibrous histiocytoma, Ewing sarcoma, eye cancer, germ cell tumor, gallbladder cancer, gastric cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor, gestational trophoblastic disease, glioma, head and neck cancer, hairy cell leukemia, hepatocellular cancer, histiocytosis, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, islet cell tumor, Kaposi sarcoma, kidney cancer, Langerhans cell histiocytosis, laryngeal cancer, leukemia, lip and oral cavity cancer, liver cancer, lobular carcinoma in situ, lung cancer, lymphoma, macroglobulinemia, malignant fibrous histiocytoma, melanoma, Merkel cell carcinoma, mesothelioma, metastatic squamous neck cancer with occult primary, midline tract carcinoma 1107368.00126 involving NUT gene, mouth cancer, multiple endocrine neoplasia syndrome, multiple myeloma, mycosis fungoides, myelodysplastic syndrome, myelodysplastic/myeloproliferative neoplasm, nasal cavity and par nasal sinus cancer, nasopharyngeal cancer, neuroblastoma, non- Hodgkin lymphoma, non-small cell lung cancer, oropharyngeal cancer, osteosarcoma, ovarian cancer, pancreatic cancer, papillomatosis, paraganglioma, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytomas, pituitary tumor, pleuropulmonary blastoma, primary central nervous system lymphoma, prostate cancer, rectal cancer, renal cell cancer, renal pelvis and ureter cancer, retinoblastoma, rhabdoid tumor, salivary gland cancer, Sezary syndrome, skin cancer, small cell lung cancer, small intestine cancer, soft tissue sarcoma, spinal cord tumor, stomach cancer, T-cell lymphoma, teratoid tumor, testicular cancer, throat cancer, thymoma and thymic carcinoma, thyroid cancer, urethral cancer, uterine cancer, vaginal cancer, vulvar cancer, and Wilms tumor. In some embodiments, the cancer is selected from breast, lung, CRC, gastric, esophageal, neuroblastoma, cervical, and hematological cancers. [00263] Any suitable autoimmune disease may be treated with the antibodies provided herein. Illustrative suitable autoimmune diseases, or diseases with an autoimmune component, include, for example, acute disseminated encephalomyelitis (ADEM), acute necrotizing hemorrhagic leukoencephalitis, Addison’s disease, agammaglobulinemia, alopecia areata, amyloidosis, ankylosing spondylitis, anti-GBM/anti-TBM nephritis, antiphospholipid syndrome (APS), autoimmune angioedema, autoimmune aplastic anemia, autoimmune dysautonomia, autoimmune hepatitis, autoimmune hyperlipidemia, autoimmune immunodeficiency, autoimmune inner ear disease (AIED), autoimmune myocarditis, autoimmune oophoritis, autoimmune pancreatitis, autoimmune retinopathy, autoimmune thrombocytopenic purpura (ATP), autoimmune thyroid disease, autoimmune urticarial, axonal & neuronal neuropathies, Balo disease, Behcet’s disease, bullous pemphigoid, cardiomyopathy, Castleman disease, Celiac disease, Chagas disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), chronic recurrent multifocal ostomyelitis (CRMO), Churg-Strauss syndrome, cicatricial pemphigoid/benign mucosal pemphigoid, Crohn’s disease, Cogans syndrome, cold agglutinin disease, colitis, congenital heart block, coxsackie myocarditis, CREST disease, essential mixed cryoglobulinemia, demyelinating neuropathies, dermatitis herpetiformis, dermatomyositis, Devic’s disease (neuromyelitis optica), discoid lupus, Dressler’s syndrome, endometriosis, eosinophilic esophagitis, eosinophilic fasciitis, erythema nodosum, experimental allergic encephalomyelitis, Evans syndrome, fibromyalgia, fibrosing alveolitis, giant cell arteritis 1107368.00126 (temporal arteritis), giant cell myocarditis, glomerulonephritis, Goodpasture’s syndrome, granulomatosis with polyangiitis (GPA) (formerly called Wegener’s Granulomatosis), Graves’ disease, Guillain-Barre syndrome, Hashimoto’s encephalitis, Hashimoto’s thyroiditis, hemolytic anemia, Henoch-Schonlein purpura, herpes gestationis, hypogammaglobulinemia, idiopathic thrombocytopenic purpura (ITP), IgA nephropathy, IgG4-related sclerosing disease, immunoregulatory lipoproteins, inclusion body myositis, inflammatory bowel disease. interstitial cystitis, juvenile arthritis, juvenile diabetes (Type 1 diabetes), juvenile myositis, Kawasaki syndrome, Lambert-Eaton syndrome, leukocytoclastic vasculitis, lichen planus, lichen sclerosus, ligneous conjunctivitis, linear IgA disease (LAD), lupus (SLE), Lyme disease (chronic), Meniere’s disease, microscopic polyangiitis, mixed connective tissue disease (MCTD), Mooren’s ulcer, Mucha-Habermann disease, multiple sclerosis, myasthenia gravis, myositis, narcolepsy, neuromyelitis optica (Devic’s), neutropenia, ocular cicatricial pemphigoid, optic neuritis, palindromic rheumatism, PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus), paraneoplastic cerebellar degeneration, paroxysmal nocturnal hemoglobinuria (PNH), Parry Romberg syndrome, Parsonnage-Turner syndrome, pars planitis (peripheral uveitis), pemphigus, peripheral neuropathy, perivenous encephalomyelitis, pernicious anemia, POEMS syndrome, polyarteritis nodosa, type I, II, & III autoimmune polyglandular syndromes, polymyalgia rheumatic, polymyositis, postmyocardial infarction syndrome, postpericardiotomy syndrome, progesterone dermatitis, primary biliary cirrhosis, rimary sclerosing cholangitis, psoriasis, psoriatic arthritis, idiopathic pulmonary fibrosis, pyoderma gangrenosum, pure red cell aplasia, Raynauds phenomenon, reactive arthritis, reflex sympathetic dystrophy, Reiter’s syndrome, relapsing polychondritis, restless legs syndrome, retroperitoneal fibrosis, rheumatic fever, rheumatoid arthritis, sarcoidosis, Schmidt syndrome, scleritis, scleroderma, Sjogren’s syndrome, sperm & testicular autoimmunity, stiff person syndrome, subacute bacterial endocarditis (SBE), Susac’s syndrome, sympathetic ophthalmia, Takayasu’s arteritis, temporal arteritis/giant cell arteritis, thrombotic disease, thrombocytopenic purpura (TTP), Tolosa-Hunt syndrome, transverse myelitis, type 1 diabetes, ulcerative colitis, undifferentiated connective tissue disease (UCTD), uveitis, vasculitis, vesiculobullous dermatosis, vitiligo, and Wegener’s granulomatosis (now termed Granulomatosis with Polyangiitis (GPA). [00264] Any suitable infection may be treated with the antibodies provided herein. Illustrative suitable infections include, for example, hepatitis A virus, hepatitis B virus, hepatitis C virus (HCV), human immunodeficiency virus (HIV), and other viral infections. 1107368.00126 [00265] Some embodiments provide for treatment of a subject suffering from cancer, a chronic infection, or from an inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of any of the antibodies set forth herein. Some embodiments provide for treatment of a subject suffering from cancer, a chronic infection, or from an inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of any of the antibodies set forth herein in combination with an effective amount of another antibody set forth herein. In some embodiments, the cancer is a hematological cancer. [00266] Some embodiments provide a method for modulating immune system function in a subject in need thereof, comprising the step of contacting a population of immune cells of the subject with a pharmaceutical composition comprising an effective amount of the antibody as set forth herein, under conditions such that the immune system is modulated. Some embodiments provide a method for modulating immune system function in a subject in need thereof, comprising the step of contacting a population of immune cells of the subject with an effective amount of any of the antibodies set forth herein in combination with an effective amount of another antibody set forth herein. In some embodiments, the antibody comprises a bispecific antibody or a complexing antibody. [00267] In some embodiments, the bispecific antibody or the complexing antibody is administered in an amount sufficient to achieve 1, 2, 3, 4, 5, 6, 7, or 8 of the following in the subject: a) inhibition of immune suppression; b) reduction of levels of regulatory T cells; c) increase an activity of myeloid cells; d) increase in activity of cytotoxic T lymphocytes, NK cells, B cells, neutrophils, monocytes, macrophages, and/or dendritic cells; e) increase in phagocytic activity; f) inhibition of metastasis; g) inhibition of tumor growth; and/or h) induction of tumor regression. [00268] In some embodiments, the bispecific antibody binds ACKR4 and a target protein. [00269] In some embodiments, the method for modulating immune system function in 1107368.00126 a subject in need thereof further comprises administering chemotherapy, administering radiation therapy, and/or administering one or more additional therapeutic agents. In some embodiments, the one or more additional therapeutic agents comprise one or more immunostimulatory agents. In some embodiments, the one or more immunostimulatory agents comprise an antagonist to an inhibitory receptor of an immune cell. In some embodiments, the inhibitory receptor is at least one of ILT2, ILT3, ILT4, KIR2DL4, CTLA-4, PD-1, CD39, CD73, PD-L1, PD-L2, LAG-3, TIGIT, B7-H3, B7-H4, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF-B, NKG2A, and/or a Killer-cell immunoglobulin-like receptor (KIR). In some embodiments, the TGF-B recepetor is LAP, GARP, and/or TGF-B traps. [00270] In some embodiments, the one or more immunostimulatory agents comprise an agonist of a co-stimulatory receptor of an immune cell. In some embodiments, the co- stimulatory receptor comprises one or more of OX40, CD2, CD27, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp30, NKp46, NKp80, CD160, and/or a CD83 ligand. [00271] In some embodiments, the one or more immunostimulatory agents comprise a cytokine. In some embodiments, the the cytokine is at least one of IL-1, IL-2, IL-5, IL-7, IL- 10, IL-12, IL-15, IL-21, and/or IL-27. In some embodiments, the one or more immunostimulatory agents comprise an oncolytic virus. In some embodiments, the oncolytic virus comprises one or more of the oncolytic virus is a Herpes simplex virus, a Vesicular stomatitis virus, an adenovirus, a Newcastle disease virus, a vaccinia virus, or a maraba virus. In some embodiments, the one or more immunostimulatory agents comprise a chimeric antigen engineered T cell. In some embodiments, immunostimulatory agents comprise a bi- or multi- specific T cell directed antibody. In some embodiments, the one or more immunostimulatory agents comprises or consists of an ADCC competent antibody that may target CD19, CD20, EGFR, Her2, SLAMF7, CD52, BCMA, GD2, CD38, or CCR4. In some embodiments, the ADCC competent antibody is effector enhanced through afucosylation, point mutations, or otherwise. [00272] In some embodiments, the one or more immunostimulatory agents comprise a bi-specific T cell engager and/or CAR-T therapy, CAR-NK therapy, CAR-macrophage therapy, adoptive T cell therapy. 11. Kits 1107368.00126 [00273] In some embodiments, an anti-ACKR4 antibody provided herein is provided in the form of a kit, i.e., a packaged combination of reagents in predetermined amounts with instructions for performing a procedure. In some embodiments, the procedure is a diagnostic assay. In other embodiments, the procedure is a therapeutic procedure. [00274] In some embodiments, the kit further comprises a solvent for the reconstitution of the anti-aCKR antibody. In some embodiments, the anti-ACKR4 antibody is provided in the form of a pharmaceutical composition. EXAMPLES Example 1: Discovery of ACKR4 Antibodies [00275] ACKR4 antibodies were discovered by the hybridoma method as first described by Kohler et al, Nature, 1975, 256:495-497 (incorporated herein by reference in its entirety) or a B cell data mining approach as provided below. The sequences and characteristics of the ACKR4 binding antibodies from these methods are provided in Table S and FIG.1. [00276] Since ACKR4 is a GPCR and reliable recombinant protein is not readily available, a genetic immunization strategy using cDNA was selected. The hACKR4 cDNA was either full length, truncated at the N-terminus by 15 amino acids, or truncated at the N-terminus by 32 amino acids. The truncated cDNA constructs were designed to focus immune responses on the membrane-proximal region of the N-terminal domain (heretofore “NTD”) and the extracellular loops (heretofore “ECLs”). Transgenic rats as described in Ma et al, J. Immunol. Methods, 2013, 400-401:78-86 (incorporated herein by reference in its entirety), “OmniRats,” were immunized with one of the three cDNA constructs and immune responses were monitored via test bleeds at day 45 post-immunization initiation. After a final boost with full length cDNA, the seropositive animals were distributed to antibody recovery by either hybridoma or B cell sequencing methods. [00277] Six animals were selected for a single hybridoma fusion and supernatants were screened by both flow cytometry and cell ELISA against cell lines engineered to overexpress ACKR4 to identify clones with the strongest binding to ACKR4 with minimal background binding to cells that did not express ACKR4. Top clones derived from hybridomas were sequenced by the Sanger sequencing method. [00278] 18 animals were chosen for a B cell mining approach that combines next generation sequencing (heretofore “NGS”), bioinformatics, and high-throughput heavy-light 1107368.00126 chain pairing and recombinant antibody expression using Teneobio’s TeneoSeek discovery platform. In brief, cryopreserved B cells were thawed, barcoded, RNA-extracted, V regions amplified, and characterized by NGS. Candidate antigen-specific sequences that showed positive selection were identified and organized into a phylogenetic tree anchored by their CDR3 sequences. Top candidates from each branch of the tree were selected as representatives and cloned into an expression vector. VH/VL sequences were paired based on the initial cell barcoding. Over 400 fully human IgG1 antibodies were expressed in HEK293 cells and screened as crude cell culture supernatants by both flow cytometry and cell ELISA.36 unique ACKR4-binding clones were identified for cloning into recombinant IgG vectors for production, purification, and screening. [00279] Purified antibodies with the lowest EC50 for ACKR4 (i.e. best binders) were then tested for their ability to inhibit the chemokine scavenging activity of ACKR4. Three antagonist clones were selected as leads and advanced to sequence optimization to remove sequence liabilities. A rational mutagenesis approach was chosen to revert unusual framework residues to germline and disrupt liabilities including hydrophobic patches and free cysteines. Example 2: Affinity Maturation of ACKR4 Antibodies [00280] The optimization of naïve, SHM variants, and/or liability-removed clones was carried out utilizing yeast display libraries selected against virus lipid particles (heretofore “VLPs”) that expressed hACKR4. All six CDRs were diversified in the affinity maturation library designs. Specific residues within each CDR were varied only to amino acids that were present in known human IgGs from each germline. Total combined heavy and light chain diversity for each lineage was greater than 1E9 variants. Selections were performed using hACKR4-VLP as the antigen with one round of bead-based MACS followed by up to six rounds of FACS. Affinity pressures were applied using decreasing concentrations of hACKR4- VLP antigen. [00281] An orthogonal approach to affinity maturation was pursued through rational mutagenesis of residues known to make critical contacts with ACKR4. This approach was enabled by obtaining a de novo cryo-EM structure of recombinant hACKR4 micelles in complex with an anti-ACKR4 Fab and anti-kappa constant region VHH nanobody that contributed to cryo-EM resolution by reducing the flexibility and increasing the mass of the complex. Ultimately, a 3.5 Å structure was obtained that showed extensive contacts between the CDRs of an anti-ACKR4 Fab and the ACKR4 NTD stump and ECL2 regions. Mutations 1107368.00126 suggested by the cryo-EM structure were combined with those obtained via affinity maturation to further enhance affinity and inhibition of scavenging activity. Example 3: Protein Expression and Purification [00282] ACKR4 IgGs and recombinant human ACKR4 full length micelles (Ala2- Ile350) (ACKR4-FL-FLAG-Avi) were expressed and purified from Expi293 cells using transient transfection with ExpiFectamine (Thermo Fisher Scientific). Enhancers were added 20 h after transfection. Cells were incubated for 5 days at 37 °C and 8% CO2. [00283] For ACKR4 IgGs, medium was collected by centrifugation at 4,000g for 20 min. ACKR4 IgGs were purified by Protein A affinity chromatography using MabSelect SuRe 5-ml column (Cytiva) and buffer exchanged into 1X PBS, pH 7.4 by dialysis. [00284] For ACKR4 micelles, medium was removed by centrifugation at 4,000g for 20 min and the Expi293 cell pellet was lysed on ice in 10 mM Tris-HCl pH 7.4, 1 mM EDTA with protease inhibitors (Roche) using a dounce tissue grinder (Kimble), centrifuged at 24,000g for 45 min at 4 °C to remove the supernatant containing cytoplasmic proteins and isolate the membrane pellet containing ACKR4. The membrane pellet was solubilized in 67 mM HEPES pH 7.4, 533 mM sodium chloride (NaCl), 1% n-Dodecyl-β-D-Maltopyranoside (DDM) (Anatrace), and 0.2% Cholesteryl Hemisuccinate Tris Salt (CHS) (Anatrace) using a dounce tissue grinder, centrifuged at 24,000g for 90 min at 4 °C to isolate the supernatant containing ACKR4, and purified by ANTI-FLAG M2 Affinity Gel (Millipore Sigma). ACKR4-FL- FLAG-Avi was further purified using SEC (Cytiva) in micelle buffer (30 mM HEPES pH 7.4, 150 mM NaCl, 10% glycerol, 0.1% DDM, and 0.02% CHS), concentrated, and flash frozen for storage at -80 °C. [00285] Purity and integrity of all proteins were assessed by HPLC and SDS-PAGE. Example 4: Cell Lines [00286] Cell lines were grown and maintained in T75 flasks at 37°C and 5% CO2. All CHO cells were grown in F12K supplemented with 10% fetal bovine serum (FBS), 1% penicillin streptomycin (Pen Strep), 1% HEPES, 1% MEM non-essential amino acids (MEM NEAA), and 1% sodium pyruvate. MC38-hACKR4, MC38-parental, SUIT2 WT, SUIT2 ACKR4 KO, AsPC-1 WT, and AsPC-1 ACKR4 KO were grown in RPMI supplemented with 10% FBS, 1% Pen Strep, 1% HEPES, 1% MEM NEAA, and 1% sodium pyruvate. Example 5: Monovalent Affinity of ACKR4 Antibody Binding to Recombinant ACKR4 1107368.00126 Micelles [00287] Binding kinetics were measured using the Octet RED96 system (ForteBio) at 30° C in micelle buffer. 2 ug/ml of ACKR4 antibody or control was immobilized onto anti- human Fc (AHC) biosensor to a binding response of approximately 0.5 nm. After a short baseline step in micelle buffer, the sensors were exposed to 200 nM ACKR4-FL-FLAG-Avi for the association step. Dissociation of the complex was monitored upon exposure of the sensors to micelle buffer for up to 10 min. Data was processed using ForteBio Octet software (v10) with negative control IgG subtraction, global fit, and 1:1 binding model to obtain association (k_on) and dissociation (k_off) rates. Equilibrium dissociation constant (KD) was calculated from the ratio of koff to kon. [00288] FIG. 1 provides a table showing recombinant ACKR4 micelle binding by ACKR4 antibodies. DNT=did not test. [00289] FIG. 2B shows sensorgram of recombinant ACKR4 micelle binding by representative ACKR4 antibodies. Data had R²> 0.9449. The association and dissociation time course data was globally fit with a simple 1:1 Langmuir binding model to yield on-rate (k_on) and off-rate (koff) values. The equilibrium dissociation constants (KD) were calculated from the ratio of k_off to k_on. Example 6: Flow Cytometry of ACKR4 Antibody Binding to Cellular ACKR4 [00290] CHO-hACKR4 cells were detached with Accutase and washed with 1X PBS. 0.1 million cells were stained with Fixable Viability Dye eFluor™ 780 (Thermo Fisher Scientific) for 30 min at 4 °C. Cells were washed with Stain Buffer (BSA) (BD Biosciences) and incubated with 0.02-400 nM (4-fold dilutions) ACKR4 antibody or control for 30 min at 4 °C. Cells were washed with Stain Buffer (BSA), fixed and permeabilized with Foxp3 / Transcription Factor Staining Buffer Set (Thermo Fisher Scientific) for 30 min at 4 °C. Cells were washed with Stain Buffer (BSA) and incubated with anti-human IgG R-Phycoerythrin (R-PE) secondary antibody (Jackson ImmunoResearch) for 30 min at 4°C. Cells were washed and resuspended with Stain Buffer (BSA). Flow cytometry was performed on BD FACSCelesta using BD FACSDiva Software (v8.0.1.1) for data acquisition. Analysis was performed using FlowJo software (v10.7.1). EC50 was calculated using GraphPad Prism (v8.3.0). [00291] FIG. 1 provides a table showing CHO-hACKR4 binding by the ACKR4 antibodies. 1107368.00126 [00292] FIG.2A shows CHO-hACKR4 binding by representative ACKR4 antibodies. Example 7: Epitope Mapping of ACKR4 Antibodies [00293] CHO-parental, CHO-hACKR4, CHO-mACKR4, ECL2 mutant (CHO- mACKR4 cells with mouse to human ECL2 mutations Q180D / T185I / H190R / S199L), and ECL3 mutant (CHO-mACKR4 cells with mouse to human ECL3 mutations Q263R / A267I / L270S / D276N) cells were detached with Accutase and washed with 1X PBS.0.05-0.1 million cells were stained with Fixable Viability Dye eFluor™ 780 (Thermo Fisher Scientific) for 30 min at 4°C. Cells were washed with Stain Buffer (BSA) (BD Biosciences) and incubated with 100 nM ACKR4 antibody for 30 min at 37 °C. Cells were washed with Stain Buffer (BSA), fixed and permeabilized with Foxp3 / Transcription Factor Staining Buffer Set (Thermo Fisher Scientific) for 30 min at 4°C. Cells were washed with Stain Buffer (BSA) and incubated with anti-human IgG allophycocyanin (APC) secondary antibody (Jackson ImmunoResearch) for 30 min at 4°C. Cells were washed and resuspended with Stain Buffer (BSA). Flow cytometry was performed on BD FACSCelesta using BD FACSDiva Software (v8.0.1.1) for data acquisition. Analysis was performed using FlowJo software (v10.7.1). [00294] FIG. 3 shows CHO ACKR4 and ECL mutant cell binding by ACKR4 antibodies. Some antibodies disclosed herein are cross-reactive binders that do not bind to ECL2 and ECL3; some antibodies bind to ECL3. Example 8: Inhibition of Chemokine Scavenging by ACKR4 Antibodies in Endogenous ACKR4 Cells [00295] Inhibition of chemokine scavenging assays were performed in polypropylene plates rather than polystyrene plates due to high non-specific binding of CCL19 and CCL21 to the polystyrene plates. Flat bottom polypropylene plates (Corning) were coated with 10 ug/ml human fibronectin (PromoCell) for 1 h at 37 °C and blocked with bovine serum albumin (BSA). 0.15 million SUIT2 WT or AsPC-1 WT cells expressing endogenous ACKR4 were plated on the fibronectin-coated plates and incubated for 5 h at 37 °C to allow the cells to become firmly attached. ACKR4 antibodies were first added to the cells followed by the chemokines CCL19 or CCL21 (R&D Systems) after 1 h. After 8-18 h incubation at 37 °C, the supernatant was removed for CCL19 or CCL21 quantification by ELISA (R&D Systems). [00296] FIG.1 provides a table showing inhibition of chemokine scavenging by ACKR4 antibodies disclosed herein. DND=did not determine. 1107368.00126 [00297] FIG. 4A and 4B show inhibition of CCL21 scavenging by representative ACKR4 antibodies in AsPC-1 WT and SUIT2 WT cells, respectively. FIG. 4C shows inhibition of CCL19 scavenging by representative ACKR4 antibodies in SUIT2 WT cells. Example 9: HiBiT Detection of ACKR4 Internalization and Down-regulation by ACKR4 Antibodies in ACKR4 Overexpressing Cells [00298] 0.05 million CHO-HiBiT-ACKR4 cells were treated with 100 ug/ml ACKR4 antibody or control in white flat bottom plate (Corning) for 4-48 h at 37° C. ACKR4 internalization and ACKR4 down-regulation were detected using Nano-Glo HiBiT Extracellular Detection System (Promega) and Nano-Glo HiBiT Lytic Detection System (Promega), respectively, following the manufacturer’s recommended protocol. HiBiT tag luminescence was measured using BioTek Gen5 software (v2.09). [00299] FIG. 5A shows extracellular luminescence of HiBiT-ACKR4 upon treatment with ACKR4 antibody or control after 15 h. FIG.5B shows % HiBiT-ACKR4 internalization by ACKR4 antibody calculated by: 100 X [1 - (RLU of treatment / RLU of Neg Ctl IgG)]. FIG. 5C and 5D show time-dependent % HiBiT-ACKR4 internalization by ACKR4 antibodies disclosed herein. FIG. 5E shows lytic luminescence of HiBiT-ACKR4 upon treatment with ACKR4 antibody or control after 15 h. FIG. 5F shows % HiBiT-ACKR4 down-regulation by ACKR4 antibody calculated by: 100 X [1 - (RLU of treatment / RLU of Neg Ctl IgG)]. Example 10: In vivo Detection of Human Backbone ACKR4 Antibodies in Mouse Serum [00300] Mice were intravenously injected with ACKR4 antibody diluted in 1X PBS at a dose volume of 200 ul per mouse. Blood was collected at pre-determined time points after injection (2 h-7 days). For mid study blood collection, mice were warmed with a heat lamp, and the tip of the tail was cut with a razorblade and ~70 ul of blood was collected into an Eppendorf tube. For the last blood collection time point, mice were euthanized by CO2 inhalation and ~300 ul of blood was collected by cardiac puncture using a 25-gauge needle within 5 min of euthanasia. Blood was allowed to clot for 45 min at room temperature and centrifuged for 12 min at room temperature at 6000 RPM in a benchtop centrifuge with a 6- inch rotor. The serum supernatant was collected with a pipette, plated in a low volume 96-well PCR plate, and stored at -80 °C until the samples were analyzed. [00301] ACKR4 antibody was measured in serum using an anti-human/non-human primate IgG MSD kit [Meso Scale Discovery (MSD)]. Serum was diluted in assay diluent to a concentration that is expected to fall within the standard curve of the assay and then ran 1107368.00126 following the manufacturer’s recommended protocol. Signal was detected using the QuickPlex SQ 120 reader (MSD), and sample quantification was interpolated from the standard curve using MSD Discovery Workbench software (v4.0.12). [00302] FIG.6A shows in vivo detection of 20 ug of ACKR4 antibodies in mouse serum of BALB/c mice after seven days. FIG.6B shows in vivo detection of 5 ug of ACKR4 antibody in mouse serum of huACKR4 KI/muACKR4 KO mice (HO) and muACKR4 wild type mice (WT) after seven days. FIG. 6C shows in vivo detection of 250 ug of ACKR4 antibodies in mouse serum of HO mice after seven days. Example 11: In vivo Detection of Inhibition of Chemokine Scavenging by ACKR4 Antibodies as Measured by CCL19 and CCL21 Levels [00303] Mice were intravenously injected with ACKR4 antibody diluted in 1X PBS at a dose volume of 200 ul per mouse. Blood was collected at pre-determined time points after injection (2 h-7 days). For mid study blood collection, mice were warmed with a heat lamp and the tip of the tail was cut with a razorblade and ~70 ul of blood was collected into an Eppendorf tube. For the last blood collection time point, mice were euthanized by CO2 inhalation and ~300 ul of blood was collected by cardiac puncture using a 25-gauge needle within 5 min of euthanasia. Blood was allowed to clot for 45 min at room temperature and centrifuged for 12 min at room temperature at 6000 RPM in a benchtop centrifuge with a 6-inch rotor. The serum supernatant was collected with a pipette, plated in a low volume 96-well PCR plate, and stored at -80°C until the samples were analyzed. [00304] Murine CCL19 and murine CCL21 were measured in serum using the Mouse CCL19 ELISA Kit (Abcam) and Mouse CCL21/6Ckine Quantikine ELISA Kit (R&D Systems), respectively. Serum was diluted in assay diluent to a concentration that is expected to fall within the standard curve of the assay and then ran following the manufacturer’s recommended protocol. Optical density was measured using the SpectraMax i3x reader (Molecular Devices), and sample quantification was interpolated from the standard curve using SoftMax 7.0 software (Molecular Devices). [00305] FIG. 7A (C57BL/6 mice), 7B [huACKR4 KI/muACKR4 KO mice (HO) and muACKR4 wild type mice (WT)], and 7C (HO mice) show murine CCL19 levels upon in vivo 250 ug ACKR4 antibody treatment after seven days. FIG. 7D (C57BL/6 mice), 7E (HO and WT mice), and 7F (HO mice) show murine CCL21 levels upon in vivo 250 ug ACKR4 antibody treatment after seven days. 1107368.00126 Example S: Sequences [00306] Table S provides sequences referred to herein. Table S Sequences. SEQ ID _{Region Scheme/Clone} ^Sequence NO: 1 CDR-H1 Kabat TCAMS 2 CDR-H1 Kabat SYGMH 3_{CDR-H1 Kabat} ^SNSDTWN 4 CDR-H1 Kabat TSAMS 5 CDR-H1 Kabat YSAMS 6 7 8 9 1₀ ₁₁ 12 CDR-H1 Chothia GFTFSTC 13 CDR-H1 Chothia GFTFSSY 1_{4 CDR-H1 Chothia} ^GDSVSSNSD 15 CDR-H1 Chothia GFTFSTS 16 CDR-H1 Chothia GFTFSYS 17 18 1₉ 20 21 2₂ 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 23 CDR-H2 Kabat AISGGGGSTYYADSVKG 24 CDR-H2 Kabat VIWYDGSNKYYADSVKG 25 CDR-H2 Kabat RTFYRSKWYNDYAVSVKS 26 27 28 29 30 31 3₂ ₃₃ 34 CDR-H2 Chothia SGGGGS 3_{5 CDR-H2 Chothia} ^WYDGSN 36 CDR-H2 Chothia FYRSKWY 3₇ 38 39 40 41 42 4₃ ₄₄ 45 CDR-H3 DPTGTTAFDY 46 CDR-H3 LRPFDY 47 CDR-H3 DIITHYYYYGMDV 48 CDR-H3 DIITHYYTYGMDV 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 49 50 51 52 5₃ ₅₄ 5^{5 CDR-L1} _RASQSVSSSLA 5^{6 CDR-L1} _{RSSQSLVYSDGNTYLN} 5^{7 CDR-L1} _{TGTSSDVGGYNYVS} 5^{8 CDR-L1} _RASQSVSRSLA 5^{9 CDR-L1} _RASQSVRRSLA 6⁰ ⁶¹ ⁶² ⁶³ ⁶⁴ ⁶⁵ 6₆ 6^{7 CDR-L2} _DASNRAT 6^{8 CDR-L2} _RVSNRDS 6^{9 CDR-L2} _AVNNRPS 7^{0 CDR-L2} _DVSNRAT 7¹ ⁷² ⁷³ 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 7⁴ ⁷⁵ ⁷⁶ 7_{7 CDR-L3} ^QQRSNWPPT 78 CDR-L3 MQGTHWPFT 79 CDR-L3 SSYTSSSTLV 80 CDR-L3 QQRSRWPPT 81 CDR-L3 QQRARWPPT 82 83 8₄ 85 8⁶ 8₇ ₈₈ 89 VH EVHLLESGGGLVQPGGSLRLSCAASGFTFSTCA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD 539 PTGTTAFDYWGQGTLVTVSS 90 VH EVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAAL 565 RPFDYWGQGTLVTVSS 91 VH QVQLQQSGPGLVQPSQTLSLTCAISGDSVSSNS DTWNWIRQSPSGGLEWLGRTFYRSKWYNDYAVS VKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC 572 ARDIITHYYYYGMDVWGQGTTVTVSS 92 VH EVHLLESGGGLVQPGGSLRLSCAASGFTFSTSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD 787, 1276, 1801 PTGTTAFDYWGQGTLVTVSS 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 93 VH QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS DTWNWIRQSPSRGLEWLGRTFYRSKWYNDYAVS VKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC 810 ARDIITHYYTYGMDVWGQGTTVTVSS 94 VH EVHLLESGGGLVQPGGSLRLSCAASGFTFSYSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD 1799 PTGTTAFDYWGQGTLVTVSS 95 96 97 9⁸ 9₉ ₁₀₀ 101 VL EIVLTQSPATLSLSPGERATLSCRASQSVSSSL AWYQQKPGQAPRLLIYDASNRATGIPARFSGSG 539 SGTDFTLTISSLEPEDFVVYYCQQRSNWPPTFG QGTKVEIK 102 VL DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSD GNTYLNWFQQRPGQSPRRLIYRVSNRDSGVPDR FSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHW 565 PFTFGPGTKVDIK 103 VL QSALTQPASVSGSPGQSITISCTGTSSDVGGYN YVSWFQQHPGKAPKLMIYAVNNRPSGVSNRFSG SKSGNTASLTISGLQAEDEADYYCSSYTSSSTL 572, 810 VFGGGTKLTVL 104 VL EIVLTQSPATLSLSPGERATLSCRASQSVSSSL AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFG 787 QGTKVEIK 105 VL EIVLTQSPATLSLSPGERATLSCRASQSVSRSL AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSRWPPTFG 1276 QGTKVEIK 1_{06 VL 1799, 1801} ^{EIVLTQSPATLSLSPGERATLSCRASQSVRRSL} AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: SGTDFTLTISSLEPEDFAVYYCQQRARWPPTFG QGTKVEIK 107 108 109 110 1₁₁ ₁₁₂ 113 hIGG4 HC EVHLLESGGGLVQPGGSLRLSCAASGFTFSTCA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD PTGTTAFDYWGQGTLVTVSSASTKGPSVFPLAP CSRSTSESTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTK TYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAP EFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVD VSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNS TYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSS IEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPV LDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHE ALHNHYTQKSLSLSPGK 539 114 hIGG1 AAA HC EVQLVESGGGVVQPGRSLRLSCAASGFTFSSYG MHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKG RFTISRDNSKNTLYLQMNSLRAEDTAVYYCAAL RPFDYWGQGTLVTVSSASTKGPSVFPLAPSSKS TSGGTAALGCLVKDYFPEPVTVSWNSGALTSGV HTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYIC NVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPE AAGAPSVFLFPPKPKDTLMISRTPEVTCVVVDV SHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPI EKTISKAKGQPREPQVYTLPPSREEMTKNQVSL TCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEA 565 LHNHYTQKSLSLSPGK 115 hIGG4 HC QVQLQQSGPGLVQPSQTLSLTCAISGDSVSSNS 572 DTWNWIRQSPSGGLEWLGRTFYRSKWYNDYAVS VKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: ARDIITHYYYYGMDVWGQGTTVTVSSASTKGPS VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPC PPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEV TCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPR EEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSN KGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNY KTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSPGK 116 hIGG1 AAA HC EVHLLESGGGLVQPGGSLRLSCAASGFTFSTSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD PTGTTAFDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV 787 MHEALHNHYTQKSLSLSPGK 117 hIGG1 AAA HC QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNS DTWNWIRQSPSRGLEWLGRTFYRSKWYNDYAVS VKSRITINPDTSKNQFSLQLNSVTPEDTAVYYC ARDIITHYYTYGMDVWGQGTTVTVSSASTKGPS VFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVS WNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPS SSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKT HTCPPCPAPEAAGAPSVFLFPPKPKDTLMISRT PEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCK VSNKALPAPIEKTISKAKGQPREPQVYTLPPSR EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE NNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGN 810 VFSCSVMHEALHNHYTQKSLSLSPGK 118 hIGG1 AAA HC EVHLLESGGGLVQPGGSLRLSCAASGFTFSTSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD 1276 PTGTTAFDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK 119 hIGG1 AAA HC EVHLLESGGGLVQPGGSLRLSCAASGFTFSYSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD PTGTTAFDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV 1799 MHEALHNHYTQKSLSLSPGK 120 hIGG1 AAA HC EVHLLESGGGLVQPGGSLRLSCAASGFTFSTSA MSWVRQAPGKGLEWVSAISGGGGSTYYADSVKG RFTISRDNSKNTLYLQMNGLRAKDTAVYYCAKD PTGTTAFDYWGQGTLVTVSSASTKGPSVFPLAP SSKSTSGGTAALGCLVKDYFPEPVTVSWNSGAL TSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQ TYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPC PAPEAAGAPSVFLFPPKPKDTLMISRTPEVTCV VVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKAL PAPIEKTISKAKGQPREPQVYTLPPSREEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTT PPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSV MHEALHNHYTQKSLSLSPGK 1801 121 122 1₂₃ 124 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 1²⁵ 1₂₆ ₁₂₇ 128 LC EIVLTQSPATLSLSPGERATLSCRASQSVSSSL AWYQQKPGQAPRLLIYDASNRATGIPARFSGSG SGTDFTLTISSLEPEDFVVYYCQQRSNWPPTFG QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH 539 QGLSSPVTKSFNRGEC 129 LC DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSD GNTYLNWFQQRPGQSPRRLIYRVSNRDSGVPDR FSGSGSGTDFTLKISRVEAEDVGVYYCMQGTHW PFTFGPGTKVDIKRTVAAPSVFIFPPSDEQLKS GTASVVCLLNNFYPREAKVQWKVDNALQSGNSQ ESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYA 565 CEVTHQGLSSPVTKSFNRGEC 130 LC QSALTQPASVSGSPGQSITISCTGTSSDVGGYN YVSWFQQHPGKAPKLMIYAVNNRPSGVSNRFSG SKSGNTASLTISGLQAEDEADYYCSSYTSSSTL VFGGGTKLTVLGQPKAAPSVTLFPPSSEELQAN KATLVCLISDFYPGAVTVAWKADSSPVKAGVET TTPSKQSNNKYAASSYLSLTPEQWKSHRSYSCQ 572, 810 VTHEGSTVEKTVAPTECS 131 LC EIVLTQSPATLSLSPGERATLSCRASQSVSSSL AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSNWPPTFG QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH 787 QGLSSPVTKSFNRGEC 132 LC EIVLTQSPATLSLSPGERATLSCRASQSVSRSL AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG SGTDFTLTISSLEPEDFAVYYCQQRSRWPPTFG QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH 1276 QGLSSPVTKSFNRGEC 133 LC _{1799, 1801} ^{EIVLTQSPATLSLSPGERATLSCRASQSVRRSL} AWYQQKPGQAPRLLIYDVSNRATGVPARFSGSG 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: SGTDFTLTISSLEPEDFAVYYCQQRARWPPTFG QGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASV VCLLNNFYPREAKVQWKVDNALQSGNSQESVTE QDSKDSTYSLSSTLTLSKADYEKHKVYACEVTH QGLSSPVTKSFNRGEC 1₃₄ 135 1₃₆ 137 1³⁸ 1₃₉ ₁₄₀ 141 Fc region for ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYF hIGG1 AAA PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVE PKSCDKTHTCPPCPAPEAAGAPSVFLFPPKPKD TLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGV EVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLN GKEYKCKVSNKALPAPIEKTISKAKGQPREPQV YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEW ESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 142 Fc region for ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYF hIGG4 PEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLS SVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVE SKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLM ISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVH NAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKE YKCKVSNKGLPSSIEKTISKAKGQPREPQVYTL PPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESN GQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW QEGNVFSCSVMHEALHNHYTQKSLSLSPGK 143 Kappa region RTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFY for LC PREAKVQWKVDNALQSGNSQESVTEQDSKDSTY SLSSTLTLSKADYEKHKVYACEVTHQGLSSPVT KSFNRGEC 1107368.00126 SEQ ID _{Region Scheme/Clone} ^Sequence NO: 144 Lambda region GQPKAAPSVTLFPPSSEELQANKATLVCLISDF for LC YPGAVTVAWKADSSPVKAGVETTTPSKQSNNKY AASSYLSLTPEQWKSHRSYSCQVTHEGSTVEKT VAPTECS 145 1₄₆ 147 MALEQNQSTDYYYEENEMNGTYDYSQYELI CIKEDVREFAKVFLPVFLTIVFVIGLAGNS MVVAIYAYYKKQRTKTDVYILNLAVADLLL LFTLPFWAVNAVHGWVLGKIMCKITSALYT LNFVSGMQFLACISIDRYVAVTKVPSQSGV GKPCWIICFCVWMAAILLSIPQLVFYTVND NARCIPIFPRYLGTSMKALIQMLEICIGFV VPFLIMGVCYFITARTLMKMPNIKISRPLK VLLTVVIVFIVTQLPYNIVKFCRAIDIIYS LITSCNMSKRMDIAIQVTESIALFHSCLNP ACKR4 ILYVFMGASFKNYVMKVAKKYGSWRRQRQS VEEFPFDSEGPTEPTSTFSI 148 149 1⁵⁰ 1₅₁ Equivalents [00307] The disclosure set forth above may encompass multiple distinct inventions with independent utility. Although each of these inventions has been disclosed in its preferred form(s), the specific embodiments thereof as disclosed and illustrated herein are not to be considered in a limiting sense, because numerous variations are possible. The subject matter of the inventions includes all novel and nonobvious combinations and subcombinations of the various elements, features, functions, and/or properties disclosed herein. The following claims particularly point out certain combinations and subcombinations regarded as novel and nonobvious. Inventions embodied in other combinations and subcombinations of features, functions, elements, and/or properties may be claimed in this application, in applications claiming priority from this application, or in related applications. Such claims, whether directed to a different invention or to the 1107368.00126 same invention, and whether broader, narrower, equal, or different in scope in comparison to the original claims, also are regarded as included within the subject matter of the inventions of the present disclosure.

Claims

1107368.00126 WHAT IS CLAIMED IS: 1. An antibody that binds specifically to a human ACKR4 (hACKR4) and is capable of 1, 2, or 3, of the following: a) inhibition of chemokine scavenging; b) ACKR4 internalization; and c) ACKR4 down-regulation. 2. The antibody of claim 1, wherein the antibody has 1, 2, 3, 4, 5, 6, or 7 of the following characteristics: a) is a monoclonal antibody; b) is a human antibody, a humanized antibody, or a chimeric antibody; c) is a bispecific antibody, a multi-specific antibody, a diabody, or a multivalent antibody; d) is of the IgG1, IgG2, IgG3, IgG4, IgA, or IgM type; e) is an antigen-binding antibody fragment; f) is a Fab fragment, a Fab' fragment, a F(ab')2 fragment, or an Fv fragment; and/or g) is a single chain antibody, a single domain antibody, or a nanobody. 3. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and a light chain variable region (VL), the VH and/or VL comprising 1, 2, 3, 4, 5, or 6 of: a) a VHCDR1 having the sequence set forth in SEQ ID NOS: 1-5 or SEQ ID NOS: 12-16, b) a VHCDR2 having the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, c) a VHCDR3 having the sequence set forth in SEQ ID NOS: 45-48, d) a VLCDR1 having the sequence set forth in SEQ ID NOS: 55-59, e) a VLCDR2 having the sequence set forth in SEQ ID NOS: 67-70, and f) a VLCDR3 having the sequence set forth in SEQ ID NOS: 77-81.

1107368.00126 4. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and a light chain variable region (VL), the VH comprising: a) a VHCDR1 having the sequence set forth in SEQ ID NOS: 1-5 or SEQ ID NOS: 12-16, b) a VHCDR2 having the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, c) a VHCDR3 having the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising: a) a VLCDR1 having the sequence set forth in SEQ ID NOS: 55-59, b) a VLCDR2 having the sequence set forth in SEQ ID NOS: 67-70, and c) a VLCDR3 having the sequence set forth in SEQ ID NOS: 77-81. 5. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and/or a light chain variable region (VL), the VH comprising at least one sequence set forth in any of SEQ ID NOS: 89-94 and the VL comprising at least one sequence set forth in any of SEQ ID NOS: 101-106. 6. An isolated nucleic acid encoding an antibody according to claim 1, claim 4, or claim 5. 7. An expression vector comprising the nucleic acid according to claim 6. 8. A prokaryotic or eukaryotic host cell comprising the vector of claim 7. 9. An oncolytic virus encoding the nucleic acid of any of claims 6-8. 10. A method for the production of a recombinant protein comprising the steps of expressing a nucleic acid according to claim 6 or claim 7 in a prokaryotic or eukaryotic host cell and recovering the protein from the cell or the cell culture supernatant. 11. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and a light chain variable region (VL),

1107368.00126 the VH comprising 1, 2, or 3 of: a) a VHCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 1-5 or 12-16, b) a VHCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, and c) a VHCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising 1, 2, or 3 of: a) a VLCDR1 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 55-59, b) a VLCDR2 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 67-70, and c) a VLCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOs 77-81. 12. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH comprising 1, 2, or 3 of: a) a VHCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 1-5 or 12-16, b) a VHCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 23-25 or SEQ ID NOS: 34-36, and c) a VHCDR3 having an amino acid sequence that is at least 90% identical to the sequence set forth in SEQ ID NOS: 45-48; and the VL comprising 1, 2, or 3 of: d) a VLCDR1 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 55-59, e) a VLCDR2 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOS: 67-70, and f) a VLCDR3 having an amino acid sequence that is homologous to the sequence set forth in SEQ ID NOs 77-81.

1107368.00126 13. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain and a light chain, the heavy chain comprising one or more molecules having a sequence consisting of one of SEQ ID NOS: 113-120 and the light chain comprising one or more molecules having a sequence consisting of one of SEQ ID NOS: 128-133. 14. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain and a light chain, a) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 113 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 128; b) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 114 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 129; c) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 115 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 130; d) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 116 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 131; e) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 117 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 130; f) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 118 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 132; g) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 119 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 133; and h) the heavy chain comprising one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 120 and the light chain comprising one or more, each molecule having a sequence consisting of SEQ ID NO: 133.

1107368.00126 15. An isolated nucleic acid encoding an antibody according to any of claims 11- 14. 16. An isolated antibody molecule capable of binding to human ACKR4 (hACKR4), comprising a heavy chain variable region (VH) and a light chain variable region (VL), VH and/or VL comprising 1, 2, 3, 4, 5, or 6 of: a) a VHCDR1 sequence comprising: (i) a Kabat CDR-H1 sequence defined by the consensus sequence Δ1-Δ2- A-M-S (SEQ ID NOS: 1 and 4-5), where Δ₁ is T or Y; and Δ₂ is C or S; or (ii) a Chothia CDR-H1 sequence defined by the consensus sequence G-F- T-F-S- Ω₆-Ω₇ (SEQ ID NOS: 12-13 and 15-16), where Ω₆ is T, S or Y; and Ω₇ is C, Y, or S; b) a VHCDR2 sequence comprising: (i) a Kabat CDR-H2 sequence defined by the consensus sequence β1-I-β3- β₄-β₅-G-β₇-β₈-β₉-Y-Y-A-D-S-V-K-G (SEQ ID NOS: 23-24) where β₁ is A or V; β3 is S or W; β4 is G or Y; β5 is G or D; β7 is S or G; β8 is N or S; and β9 is T or K.; or (ii) a Chothia CDR-H2 sequence defined by the consensus sequence ε₁-ε₂- ε3-G- ε5-ε6 (SEQ ID NOS: 34-35), where ε1 is S or W; ε2 is G or Y; ε3 is G or D; ε₅ is G or S; and ε₆ is S or N; c) a VHCDR3 sequence comprising: (i) a CDR-H3 sequence defined by the consensus sequence D-I-I-T-H-Y- Y-У8-Y-G-M-D-V (SEQ ID NOS: 47-48), where У8 is Y or T; d) a VLCDR1 sequence comprising: (i) a CDR-L1 sequence defined by the consensus sequence R-A-A-Q-S-V- ϕ₇-ϕ₈-S-L-A (SEQ ID NOS: 55 and 58-59), where ϕ₇ is S or R; and ϕ₈ is S or R; e) a VLCDR2 sequence comprising: (i) a CDR-L2 sequence defined by the consensus sequence ψ₁- ψ₂- ψ₃-N- R- ψ6-ψ7 (SEQ ID NOS: 67-70), where ψ1 is D, R, or A; ψ2 is V or A; ψ3 is N or

1107368.00126 S; ψ6 is A, D or P; and ψ7 is T or S, and f) a VLCDR3 sequence comprising: (i) a CDR-L3 sequence defined by the consensus sequence π1- Q-π3-π4- π5- W-P- π₈-T (SEQ ID NOS: 77-78 and 80-81), where π₁ is Q or M; π₃ is R or G; π4 is T, S, or A; π5.is N, H, or R; and π8 is P or F.