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NZ735778B2 - Kappa myeloma antigen chimeric antigen receptors and uses thereof - Google Patents

Kappa myeloma antigen chimeric antigen receptors and uses thereof Download PDF

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Publication number
NZ735778B2
NZ735778B2 NZ735778A NZ73577816A NZ735778B2 NZ 735778 B2 NZ735778 B2 NZ 735778B2 NZ 735778 A NZ735778 A NZ 735778A NZ 73577816 A NZ73577816 A NZ 73577816A NZ 735778 B2 NZ735778 B2 NZ 735778B2
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NZ
New Zealand
Prior art keywords
car
domain
chain
cell
genetically modified
Prior art date
Application number
NZ735778A
Other versions
NZ735778A (en
Inventor
Rosanne Dunn
David Gottlieb
Grant Logan
Kenneth Micklethwaite
Original Assignee
Haemalogix Pty Ltd
Filing date
Publication date
Application filed by Haemalogix Pty Ltd filed Critical Haemalogix Pty Ltd
Priority claimed from PCT/US2016/029203 external-priority patent/WO2016172703A2/en
Publication of NZ735778A publication Critical patent/NZ735778A/en
Publication of NZ735778B2 publication Critical patent/NZ735778B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/14—Blood; Artificial blood
    • A61K35/17—Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/204—IL-6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/4611—
    • A61K39/4631—
    • A61K39/4644—
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5412—IL-6
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5434—IL-12
    • 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
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • 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
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • 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
    • C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
    • 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
    • C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/526—CH3 domain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • 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
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/035—Fusion polypeptide containing a localisation/targetting motif containing a signal for targeting to the external surface of a cell, e.g. to the outer membrane of Gram negative bacteria, GPI- anchored eukaryote proteins
    • 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
    • C12N2510/00—Genetically modified 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
    • C12N5/06—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

Abstract

The present invention provides compositions and methods for treating KMA-expressing malignancies including chimeric antigen receptors (CARs) and T cells containing CARs (CAR T-cells). The invention also provides methods and compositions comprising CAR T-cells co-expressing other anti-tumoral agents including cytokines and antibodies.

Claims (18)

What is claimed is:
1. A chimeric antigen receptor (CAR) comprising one or more intracellular signaling domains and an extracellular antigen binding domain, wherein the extracellular antigen binding domain comprises a single chain variable fragment (scFv), wherein the scFv comprises complementarity determining regions (CDRs) derived from a Kappa monoclonal antibody (KappaMab), and wherein the KappaMAb CDRs comprise SEQ ID NOS: 3-8.
2. The CAR of claim 1, wherein the one or more intracellular signaling domains comprises one or more co-stimulatory endodomains.
3. The CAR of claim 2, wherein the one or more co-stimulatory endodomains is one or more of a CD28 domain, a CD3 ? domain, a 4-1BB domain and an OX-40 domain or combinations thereof.
4. The CAR of any one of claims 1 to 3, wherein the scFv comprises the VL chain and VH chain from the KappaMab, and wherein the VL chain comprises SEQ ID NO: 21 and a VH chain comprises SEQ ID NO: 22.
5. The CAR of claim 4, wherein the VL chain and the VH chain from the KappaMab are attached via a glycine-serine linker, and wherein the glycine-serine linker is a 15 amino acid linker comprising (Gly Ser) .
6. The CAR according to any one of claims 1 to 5, wherein the scFv is attached to the one or more intracellular signaling domains via a spacer, and wherein the spacer is an immunoglobulin constant region or a CD8 ? chain.
7. The CAR of claim 6, wherein the immunoglobulin constant region comprises one or more of an IgG hinge domain, an IgG CH2 domain and an IgG CH3 domain.
8. The CAR according to claim 6 or claim 7, wherein the spacer is attached to the scFV via a glycine-serine linker, and wherein the glycine-serine linker is a 15 amino acid linker comprising (Gly Ser) 4 3..
9. An isolated genetically modified T cell engineered to express the CAR of any one of claims 1 to 8.
10. The isolated genetically modified T cell of claim 9, further engineered to express one or more additional biological molecules.
11. The isolated genetically modified T cell of claim 9 or claim 10, wherein the one or more additional biological molecules comprises one or more of IL-12, an hepatocyte growth factor (HGF binding protein), Galectin-3C (GAL3C) and SANT7.
12. A method for producing an isolated genetically modified T cell according to any one of claims 9 to 11, the method comprising introducing an expression vector encoding a CAR comprising one or more intracellular signaling domain and an extracellular antigen binding domain, wherein the extracellular antigen binding domain specifically recognizes kappa myeloma antigen (KMA) into a T cell.
13. The method of claim 12, wherein the expression vector is a viral vector expression system.
14. Use of a genetically modified T cell according to any one of claims 9 to 11 in the manufacture of a medicament for treating a KMA-expressing malignancy in a subject in need thereof.
15. The use of claim 14, wherein the KMA-expressing malignancy is multiple myeloma, Waldenstroms macroglobulinemia, diffuse large B cell lymphoma (DLBCL), or amyloidosis.
16. The use of claim 14 or claim 15, wherein the medicament is provided for administration with one or more pharmaceutically active agents.
17. The use according claim 16, wherein the one or more pharmaceutically active agents comprise one or more of a chemotherapeutic agent, an immunomodulatory drug and a histone deacetylase inhibitor.
18. The use according any one of claims 14 to 17, wherein the genetically modified T cells are derived from the subject. fsi-w vatv JsXXXS; -r-'^ awete •;< : - JSSk' .wv-v^ am**®®® iSSMSSW ******«•»»»«, ^XvVXvV---,- $T JJN-3 Pfeiffer NCI-H929 RPMI-8226 NALM-6 MOLT-4 n f/n $ ii i t II :fA / / » 1 A
NZ735778A 2016-04-25 Kappa myeloma antigen chimeric antigen receptors and uses thereof NZ735778B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562151968P 2015-04-23 2015-04-23
US201562158407P 2015-05-07 2015-05-07
PCT/US2016/029203 WO2016172703A2 (en) 2015-04-23 2016-04-25 Kappa myeloma antigen chimeric antigen receptors and uses thereof

Publications (2)

Publication Number Publication Date
NZ735778A NZ735778A (en) 2024-03-22
NZ735778B2 true NZ735778B2 (en) 2024-06-25

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