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NZ770737B2 - BCMA Chimeric antigen receptors - Google Patents

BCMA Chimeric antigen receptors Download PDF

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Publication number
NZ770737B2
NZ770737B2 NZ770737A NZ77073715A NZ770737B2 NZ 770737 B2 NZ770737 B2 NZ 770737B2 NZ 770737 A NZ770737 A NZ 770737A NZ 77073715 A NZ77073715 A NZ 77073715A NZ 770737 B2 NZ770737 B2 NZ 770737B2
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NZ
New Zealand
Prior art keywords
cell
immune effector
effector cell
vivo
bcma
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NZ770737A
Other versions
NZ770737A (en
Inventor
Kevin Friedman
Richard Morgan
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Seventy Bio Inc
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Publication date
Application filed by Seventy Bio Inc filed Critical Seventy Bio Inc
Priority claimed from NZ733025A external-priority patent/NZ733025A/en
Publication of NZ770737A publication Critical patent/NZ770737A/en
Publication of NZ770737B2 publication Critical patent/NZ770737B2/en

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    • 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
    • C07K14/70503—Immunoglobulin superfamily
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    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
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    • 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
    • C07K16/2878—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-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
    • C—CHEMISTRY; METALLURGY
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    • 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
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K2319/00—Fusion polypeptide
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    • 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
    • C07K2319/32—Fusion polypeptide fusions with soluble part of a cell surface receptor, "decoy receptors"
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    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
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    • C12N15/86—Viral vectors
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    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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    • C12N2830/00—Vector systems having a special element relevant for transcription
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    • C12N5/0602—Vertebrate cells
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    • C12N5/0636—T lymphocytes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Abstract

The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides for use of the chimeric antigen receptor in adoptive T cell therapies for B cell related conditions. In a particular embodiment the invention is a lentiviral vector comprising a left (5') lentiviral LTR wherein the promoter of the 5' LTR is replaced with a CMV promoter; a Psi (?) packaging signal; a cPPT/FLAP; a Rev response element (RRE); a myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a polynucleotide encoding a B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) comprising the amino acids 22-493 of SEQ ID NO: 9; a right (3') lentiviral self-inactivating (SIN) LTR; and a heterologous polyadenylation sequence. The BCMA CAR contains a promoter, the variable light and variable heavy regions of the anti-BCMA antibody C11D5.3 linked to a CD8 hinge region, 4-1BB and CD3 Zeta; wherein the CD8 hinge region is truncated. A further embodiment includes the use of an immune effector cell, such as a T-lymphocyte or a natural killer (NK) cell, which expresses the lentiviral vector for use in the treatment of B cell lymphoma or multiple myeloma.

Claims (15)

1. A lentiviral vector sing a left (5') lentiviral LTR n the promoter of the 5' LTR is replaced with a CMV promoter; a Psi (?) packaging signal; a cPPT/FLAP; a Rev response element (RRE); a myeloproliferative sarcoma virus er, negative control region deleted, dl587rev primer-binding site substituted (MND) promoter operably linked to a polynucleotide encoding a chimeric antigen receptor (CAR) comprising the amino acids 22- 493 of SEQ ID NO: 9; a right (3') lentiviral self-inactivating (SIN) LTR; and a heterologous polyadenylation sequence.
2. The lentiviral vector of claim 1, wherein the CAR comprises the amino acid sequence set forth in SEQ ID NO: 9.
3. The lentiviral vector of claim 1 or claim 2, wherein the polynucleotide sequence encoding the CAR comprises the sequence set forth in SEQ ID NO: 10.
4. The lentiviral vector of any one of claims 1-3, wherein the iral vector is selected from the group consisting essentially of: human immunodeficiency virus 1 (HIV-1); human immunodeficiency virus 2 (HIV-2); visna-maedi virus (VMV) virus; e arthritisencephalitis virus (CAEV); equine infectious anemia virus (EIAV); feline immunodeficiency virus (FIV); bovine immune deficiency virus (BIV); and simian immunodeficiency virus (SIV).
5. The lentiviral vector of any one of claims 1-4, wherein the heterologous polyadenylation ce is a bovine growth hormone polyadenylation signal or a rabbit ß- globin polyadenylation sequence.
6. An ex vivo or in vitro immune effector cell comprising the iral vector of any one of claims 1-5.
7. The ex vivo or in vitro immune effector cell of claim 6, wherein the immune or cell is selected from the group consisting of: a T lymphocyte and a natural killer (NK) cell.
8. The ex vivo or in vitro immune effector cell of claim 6 or claim 7, wherein the immune effector cell is a T lymphocyte.
9. The ex vivo or in vitro immune effector cell of claim 6 or claim 7, wherein the immune effector cell is an NK cell.
10. A composition comprising the ex vivo or in vitro immune effector cell of any one of claims 6-9.
11. A composition comprising the ex vivo or in vitro immune effector cell of any one of claims 6-9 and a physiologically able ent.
12. Use of the ex vivo or in vitro immune effector cell of any one of claims 6-9 in the manufacture of a medicament for the treatment of multiple myeloma.
13. Use of the ex vivo or in vitro immune effector cell of any one of claims 6-9 in the manufacture of a medicament for the treatment of B cell lymphoma.
14. Use of the composition of claim 10 or claim 11 in the manufacture of a medicament for the treatment of multiple myeloma.
15. Use of the composition of claim 10 or claim 11 in the manufacture of a ment for the treatment of B cell lymphoma. 1 /23 E 3:: SUBSTITUTE SHEET (RULE 26) hIFN—y e + BCMA02 -—I—- BCMA1O —-t-— CAR19A huIFNy [ng/ml] 1 10 100 1000 SBCMA [ng/ml] SUBSTITUTE SHEET (RULE 26) thN-y Release BCMA—02 BCMA—10 - CAR19A IFN-y in co-cullure wilh control cell line SUBSTITUTE SHEET (RULE 26) °Ve LOD 10000 E§§§ Unhunsduced 3 1500 32:13.12 BCMA 10]P 19171 I“ IFNg TNFa |L-1b |L-6 SUBSTITUTE SHEET (RULE 26) 500.on 31.: _H 5: 5% Siam Siam ml: cozsoom Soow § E I E 3-: 0:30.— m__8 o £5 .50: ES .vN #8 ml: a 3&2 coon coo.“~ ooom ooom coo— Iw/?d SUBSTITUTE SHEET (RULE 26) 2.43% 8:8 $320 g 2 I \
NZ770737A 2015-12-07 BCMA Chimeric antigen receptors NZ770737B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462091419P 2014-12-12 2014-12-12
US201562200505P 2015-08-03 2015-08-03
NZ733025A NZ733025A (en) 2014-12-12 2015-12-07 Bcma chimeric antigen receptors

Publications (2)

Publication Number Publication Date
NZ770737A NZ770737A (en) 2024-07-05
NZ770737B2 true NZ770737B2 (en) 2024-10-08

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