NZ762829B2 - Novel anti-hla-a2 antibodies and uses thereof - Google Patents

Novel anti-hla-a2 antibodies and uses thereof

Info

Publication number
NZ762829B2
NZ762829B2 NZ762829A NZ76282918A NZ762829B2 NZ 762829 B2 NZ762829 B2 NZ 762829B2 NZ 762829 A NZ762829 A NZ 762829A NZ 76282918 A NZ76282918 A NZ 76282918A NZ 762829 B2 NZ762829 B2 NZ 762829B2
Authority
NZ
New Zealand
Prior art keywords
antibody
antigen
binding fragment
domain
hla
Prior art date
Application number
NZ762829A
Other versions
NZ762829A (en
Inventor
Tobias Abel
Nicolas Dawson
Caroline Lamarche
Megan Levings
Francois Meyer
Li Zhou
Original Assignee
Sangamo Therapeutics France
The University Of British Columbia
Filing date
Publication date
Application filed by Sangamo Therapeutics France, The University Of British Columbia filed Critical Sangamo Therapeutics France
Priority claimed from PCT/CA2018/051174 external-priority patent/WO2019056106A1/en
Publication of NZ762829A publication Critical patent/NZ762829A/en
Publication of NZ762829B2 publication Critical patent/NZ762829B2/en

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    • 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
    • A61K2035/122—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells for inducing tolerance or supression of immune responses
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5156—Animal cells expressing foreign proteins
    • 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
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2121/00—Preparations for use in therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • 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
    • 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
    • A61K40/20—Cellular immunotherapy characterised by the effect or the function of the cells
    • A61K40/22—Immunosuppressive or immunotolerising
    • 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
    • A61K40/418—Antigens related to induction of tolerance to non-self
    • 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
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • C07K14/70517—CD8
    • 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
    • C07K16/2833—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 against MHC-molecules, e.g. HLA-molecules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • 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
    • 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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/60—Fusion polypeptide containing spectroscopic/fluorescent detection, e.g. green fluorescent protein [GFP]
    • 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
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/62—DNA sequences coding for fusion proteins

Abstract

The present invention relates to a novel anti-HLA-A2 antibody, and to a chimeric antigen receptor comprising said HLA-A2 antibody. The present invention further relates to an immune cell expressing said chimeric receptor antigen, and to therapeutic uses thereof, in particular for treating or preventing graft rejection or GVHD.

Claims (18)

1. A humanized anti-HLA-A2 antibody, or an antigen-binding fragment thereof, wherein said antibody or antigen-binding fragment f comprises a heavy chain 5 variable domain (VH) and a light chain variable domain (VL), wherein the amino acid sequence of the VH ses SEQ ID NO: 9 and wherein the amino acid sequence of the VL comprises SEQ ID NO: 13.
2. The humanized anti-HLA-A2 antibody or antigen-binding fragment according to claim 1, wherein said antibody or antigen-binding fragment is a whole antibody, a 10 single chain antibody, a dimeric single chain antibody, a Fv, a scFv, a Fab, a F(ab)'2, a defucosylated antibody, a bi-specific antibody, a diabody, a triabody, a tetrabody, or a unibody.
3. The humanized anti-HLA-A2 antibody or antigen-binding fragment according to claim 1 or 2, wherein said antibody or antigen-binding fragment is a scFv. 15
4. The humanized anti-HLA-A2 dy or antigen-binding fragment according to any one of claims 1 to 3, wherein said antibody or antigen-binding fragment is a scFv comprising the amino acid sequence of SEQ ID NO: 72.
5. A chimeric antigen receptor (CAR) sing: a) an ellular domain comprising the humanized anti-HLA-A2 antibody or 20 antigen-binding fragment according to any one of claims 1 to 4, b) a embrane ; and c) a asmic domain comprising an intracellular signaling domain.
6. The CAR according to claim 5, wherein the humanized anti-HLA-A2 antibody or antigen-binding nt is an scFv comprising the amino acid sequence of SEQ 25 ID NO: 72.
7. The CAR according to claim 5 or 6, wherein the CAR specifically binds to HLAA *02:01. 1005738693
8. The CAR according to any one of claims 5 to 7, wherein the embrane domain is a CD8 transmembrane domain and the intracellular ing domain comprises a 4-1BB costimulatory domain and a CD3 zeta primary signaling domain.
9. A nucleic acid molecule encoding the CAR according to any one of claims 5 to 8. 5
10. A vector comprising the nucleic acid molecule of claim 9.
11. An isolated regulatory immune cell sing the CAR according to any one of claims 5 to 8 or the c acid molecule according to claim 9 or the vector according to claim 10.
12. The isolated regulatory immune cell according to claim 11, wherein said immune 10 cell is a regulatory T cell.
13. A pharmaceutical ition sing isolated regulatory immune cells according to claims 11 or claim 12 and a pharmaceutically acceptable excipient.
14. Use of a chimeric antigen receptor according to any one of claims 5 to 8, a nucleic acid molecule according to claim 9, of a vector according to claim 10, an isolated 15 regulatory immune cell ing to claim 11 or claim 12, or the pharmaceutical composition of claim 13, in the manufacture of a medicament for inducing immune tolerance.
15. The use according to claim 14, wherein said immune tolerance is tolerance to a transplanted organ or tissue. 20
16. Use of a chimeric antigen receptor according to any one of claims 5 to 8, a nucleic acid molecule according to claim 9, a vector according to claim 10, an isolated regulatory immune cell according to claim 11 or claim 12, or the pharmaceutical composition of claim 13, in the manufacture of a medicament for treating organ or tissue transplant rejection or graft versus host e (GVHD). 25
17. Use of a combination of an isolated regulatory immune cell according to claim 11 or claim 12, or the pharmaceutical composition of claim 13, with at least one immunosuppressive agent, in the manufacture of a medicament for inducing 1005738693 immune tolerance, or for treating organ or tissue transplant rejection or graft versus host e (GVHD).
18. A kit of parts comprising, in a first part, an isolated regulatory immune cell according to claim 11 or claim 12 or a pharmaceutical composition according to 5 claim 13, and in a second part at least one immunosuppressive agent. 1005738693 ?asco; z 535:8 3:0 mg mammm O. I 4 can mh C) m mN 3“!P“l¢t amalau % :22ch mg‘m?é 53:28 wco? «EU mnmmm . I 4 omao.raoméwaoawaw209%?aowaomeoa?a?aao?ammofow aawoawae?ozaaz eowaoweo?.????????????..$$$$$$$$$$$%% an: mm D L? mm Sugpugq anilElahl ‘36
NZ762829A 2018-09-20 Novel anti-hla-a2 antibodies and uses thereof NZ762829B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201762560841P 2017-09-20 2017-09-20
US201862691027P 2018-06-28 2018-06-28
PCT/CA2018/051174 WO2019056106A1 (en) 2017-09-20 2018-09-20 Novel anti-hla-a2 antibodies and uses thereof

Publications (2)

Publication Number Publication Date
NZ762829A NZ762829A (en) 2025-02-28
NZ762829B2 true NZ762829B2 (en) 2025-06-04

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