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GB2607716A - Targeting B cell activating factor receptor (BAFF-R) using ligand-based chimeric antigen receptor (CAR)-T cells - Google Patents

Targeting B cell activating factor receptor (BAFF-R) using ligand-based chimeric antigen receptor (CAR)-T cells Download PDF

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Publication number
GB2607716A
GB2607716A GB2206128.7A GB202206128A GB2607716A GB 2607716 A GB2607716 A GB 2607716A GB 202206128 A GB202206128 A GB 202206128A GB 2607716 A GB2607716 A GB 2607716A
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immune cell
receptor
variant
cell
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GB2607716B (en
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Parameswaran Reshmi
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Case Western Reserve University
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Case Western Reserve University
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Priority claimed from US16/888,989 external-priority patent/US12023354B2/en
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/10—Cellular immunotherapy characterised by the cell type used
    • A61K40/11—T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/30—Cellular immunotherapy characterised by the recombinant expression of specific molecules in the cells of the immune system
    • A61K40/31—Chimeric antigen receptors [CAR]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4202—Receptors, cell surface antigens or cell surface determinants
    • A61K40/4214—Receptors for cytokines
    • A61K40/4215—Receptors for tumor necrosis factors [TNF], e.g. lymphotoxin receptor [LTR], CD30
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K40/00—Cellular immunotherapy
    • A61K40/40—Cellular immunotherapy characterised by antigens that are targeted or presented by cells of the immune system
    • A61K40/41—Vertebrate antigens
    • A61K40/42—Cancer antigens
    • A61K40/4231—Cytokines
    • A61K40/4232—Tumor necrosis factors [TNF] or CD70
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70575—NGF/TNF-superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0638—Cytotoxic T lymphocytes [CTL] or lymphokine activated killer cells [LAK]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0646—Natural killers cells [NK], NKT cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/10—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the structure of the chimeric antigen receptor [CAR]
    • A61K2239/11—Antigen recognition domain
    • A61K2239/15—Non-antibody based
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/31—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterized by the route of administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/38—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the dose, timing or administration schedule
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2239/00—Indexing codes associated with cellular immunotherapy of group A61K40/00
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K40/00 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
    • C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
    • C07K2317/622—Single chain antibody (scFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
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    • C12N2510/00—Genetically modified cells
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes

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  • Pharmacology & Pharmacy (AREA)
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  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
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Abstract

The disclosure relates generally to ligand-based chimeric antigen receptor (CAR) cells. More specifically, the CAR cells express B-cell activating factor (BAFF) protein for recognition by a receptor of BAFF on the surface of a cell. CAR cells can include cytotoxic T lymphocytes, natural killer (NK) cells or natural killer T (NKT) cells that express a chimeric receptor that recognizes a receptor of BAFF. The disclosure further relates to methods of treating a variety of conditions, such as cancers and autoimmune diseases, using the disclosed CAR cells.

Claims (20)

What is claimed is:
1. An immune cell expressing a chimeric antigen receptor that recognizes a receptor of B-cell activating factor (BAFF), wherein the immune cell is selected from cytotoxic T lymphocytes, natural killer cells, and natural killer T cells, and the chimeric antigen receptor is selected from the group consisting of SEQ ID NO: 18, a variant having 95% or greater sequence homology with SEQ ID NO: 18; SEQ ID NO: 19, a variant having 95% or greater sequence homology with SEQ ID NO: 19; SEQ ID NO: 20, and a variant having 95% or greater sequence homology with SEQ ID NO: 20.
2. The immune cell of claim 1, wherein the chimeric antigen receptor further comprises a signaling peptide.
3. The immune cell of claim 2, wherein the chimeric antigen receptor is selected from the group consisting of SEQ ID NO: 21, a variant having 95% or greater sequence homology with SEQ ID NO: 21; SEQ ID NO: 22, a variant having 95% or greater sequence homology with SEQ ID NO: 22; SEQ ID NO: 23, and a variant having 95% or greater sequence homology with SEQ ID NO: 23.
4. The immune cell of claim 1 , wherein the immune cell is isolated from a human.
5. The immune cell of claim 1, wherein the immune cell is a cytotoxic T lymphocyte.
6. The immune cell of claim 1, wherein the immune cell is a natural killer cell or a natural killer T cell.
7. The immune cell of claim 1, wherein the receptor of BAFF is selected from the group consisting of B-cell maturation antigen, transmembrane activator and CAML interactor, and BAFF receptor.
8. A method of treating a patient in need thereof, comprising administering to the patient an therapeutically effective amount of a composition comprising an immune cell expressing a chimeric antigen receptor that recognizes a receptor of B-cell activating factor (BAFF), wherein the immune cell is selected from cytotoxic T lymphocytes, natural killer cells, and natural killer T cells, and the chimeric antigen receptor is selected from the group consisting of SEQ ID NO: 18, a variant having 95% or greater sequence homology with SEQ ID NO: 18; SEQ ID NO: 19, a variant having 95% or greater sequence homology with SEQ ID NO: 19; SEQ ID NO: 20, and a variant having 95% or greater sequence homology with SEQ ID NO: 20.
9. The method of claim 8, wherein the patient has been diagnosed with cancer.
10. The method of claim 9, wherein the cancer is a hematological malignancy.
11. The method of claim 10, wherein the hematological malignancy is leukemia.
12. The method of claim 8, wherein the patient has been diagnosed with an autoimmune disease.
13. The method of claim 12, wherein the autoimmune disease is selected from systemic lupus erythematosus, Sjorgenâ s syndrome, narcolepsy, diabetes, pancreatitis, Crohnâ s disease, celiac disease, ankylosing spondylitis, psoriasis, Graveâ s disease, and rheumatoid arthritis.
14. The method of claim 8, wherein the composition is co-administered with one or more chemotherapeutic agents.
15. The method of claim 8, wherein the chimeric antigen receptor further comprises a signaling peptide.
16. The method of claim 15, wherein the chimeric antigen receptor is selected from the group consisting of SEQ ID NO: 21, a variant having 95% or greater sequence homology with SEQ ID NO: 21; SEQ ID NO: 22, a variant having 95% or greater sequence homology with SEQ ID NO: 22; SEQ ID NO: 23, and a variant having 95% or greater sequence homology with SEQ ID NO: 23.
17. The method of claim 8, wherein the immune cell is isolated from a human.
18. The method of claim 8, wherein the immune cell is a cytotoxic T lymphocyte.
19. The method of claim g, wherein the immune cell is a natural killer cell or a natural killer T cell.
20. The method of claim g, wherein the receptor of BAFF is selected from the group consisting of B-cell maturation antigen, transmembrane activator and CAML interactor, and BAFF receptor.
GB2206128.7A 2019-10-01 2020-11-30 Targeting B cell activating factor receptor (BAFF-R) using ligand-based chimeric antigen receptor (CAR)-T cells Active GB2607716B (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201962908795P 2019-10-01 2019-10-01
US202062980727P 2020-02-24 2020-02-24
US16/888,989 US12023354B2 (en) 2019-05-31 2020-06-01 Targeting B cell activating factor receptor (BAFF-R) using ligand-based chimeric antigen receptor (CAR)-T cells
PCT/IB2020/061294 WO2021064718A1 (en) 2019-10-01 2020-11-30 Targeting b cell activating factor receptor (baff-r) using ligand-based chimeric antigen receptor (car)-t cells

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GB202206128D0 GB202206128D0 (en) 2022-06-08
GB2607716A true GB2607716A (en) 2022-12-14
GB2607716B GB2607716B (en) 2024-10-30

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EP (1) EP4041294A4 (en)
AU (2) AU2020358483A1 (en)
GB (1) GB2607716B (en)
WO (1) WO2021064718A1 (en)

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WO2018132513A1 (en) * 2017-01-10 2018-07-19 The General Hospital Corporation T cells experessing a chimeric antigen receptor
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US20200376032A1 (en) * 2019-05-31 2020-12-03 Case Western Reserve University Targeting b cell activating factor receptor (baff-r) using ligand-based chimeric antigen receptor (car)-t cells

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WO2018132513A1 (en) * 2017-01-10 2018-07-19 The General Hospital Corporation T cells experessing a chimeric antigen receptor
WO2018237022A1 (en) * 2017-06-21 2018-12-27 Icell Gene Therapeutics Llc Chimeric antigen receptors (cars), compositions and methods thereof
US20200376032A1 (en) * 2019-05-31 2020-12-03 Case Western Reserve University Targeting b cell activating factor receptor (baff-r) using ligand-based chimeric antigen receptor (car)-t cells

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TURAZZI, N., et al., "Engineered T cells towards TNFRSF13C (BAFFR) : a novel strategy to efficiently target B-cell acute lymphoblastic leukaemia", British Journal of Haematology, September 2018, Volume 182, Number 6, Pages 939-943. Whole document. *

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AU2025203549A1 (en) 2025-06-12
EP4041294A1 (en) 2022-08-17
GB202206128D0 (en) 2022-06-08
EP4041294A4 (en) 2024-10-02
WO2021064718A1 (en) 2021-04-08
AU2020358483A1 (en) 2022-05-26
GB2607716B (en) 2024-10-30

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