CN105384825B - 一种基于单域抗体的双特异性嵌合抗原受体及其应用 - Google Patents

一种基于单域抗体的双特异性嵌合抗原受体及其应用 Download PDF

Info

Publication number
CN105384825B
CN105384825B CN201510733585.2A CN201510733585A CN105384825B CN 105384825 B CN105384825 B CN 105384825B CN 201510733585 A CN201510733585 A CN 201510733585A CN 105384825 B CN105384825 B CN 105384825B
Authority
CN
China
Prior art keywords
single domain
car
antigen receptor
domain antibody
cell
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201510733585.2A
Other languages
English (en)
Other versions
CN105384825A (zh
Inventor
范晓虎
周传初
庄秋传
王平艳
王林
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nanjing Legend Biotechnology Co Ltd
Original Assignee
Nanjing Legend Biotechnology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nanjing Legend Biotechnology Co Ltd filed Critical Nanjing Legend Biotechnology Co Ltd
Priority to CN201510733585.2A priority Critical patent/CN105384825B/zh
Publication of CN105384825A publication Critical patent/CN105384825A/zh
Priority to CR20210225A priority patent/CR20210225A/es
Priority to CA2994579A priority patent/CA2994579C/en
Priority to MX2018001739A priority patent/MX2018001739A/es
Priority to EP22168161.2A priority patent/EP4063397A1/en
Priority to PCT/CN2016/094408 priority patent/WO2017025038A1/en
Priority to US15/751,609 priority patent/US10934363B2/en
Priority to SG10201913485QA priority patent/SG10201913485QA/en
Priority to IL257297A priority patent/IL257297B/en
Priority to KR1020187006996A priority patent/KR20180035918A/ko
Priority to NZ758571A priority patent/NZ758571A/en
Priority to IL294683A priority patent/IL294683A/en
Priority to BR112018002844-4A priority patent/BR112018002844A2/pt
Priority to JP2018526984A priority patent/JP6859347B2/ja
Priority to EP16834662.5A priority patent/EP3334765A4/en
Priority to MYPI2018000199A priority patent/MY188362A/en
Priority to EA201890302A priority patent/EA201890302A1/ru
Priority to CR20180153A priority patent/CR20180153A/es
Priority to UAA201802367A priority patent/UA125818C2/uk
Priority to AU2016305075A priority patent/AU2016305075B2/en
Priority to ZA2018/00703A priority patent/ZA201800703B/en
Priority to MX2022015823A priority patent/MX2022015823A/es
Priority to CL2018000378A priority patent/CL2018000378A1/es
Priority to PH12018500295A priority patent/PH12018500295A1/en
Priority to SA518390904A priority patent/SA518390904B1/ar
Priority to CONC2018/0001405A priority patent/CO2018001405A2/es
Application granted granted Critical
Publication of CN105384825B publication Critical patent/CN105384825B/zh
Priority to AU2020200151A priority patent/AU2020200151C1/en
Priority to US17/164,125 priority patent/US20210261675A1/en
Priority to JP2021052453A priority patent/JP7168173B2/ja
Priority to CL2021001686A priority patent/CL2021001686A1/es
Priority to AU2022204180A priority patent/AU2022204180A1/en
Priority to JP2022167222A priority patent/JP2022183283A/ja
Priority to JP2024014929A priority patent/JP2024032975A/ja
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • 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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/461—Cellular immunotherapy characterised by the cell type used
    • A61K39/4611—T-cells, e.g. tumor infiltrating lymphocytes [TIL], lymphokine-activated killer cells [LAK] or regulatory T cells [Treg]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/463—Cellular immunotherapy characterised by recombinant expression
    • A61K39/4631—Chimeric Antigen Receptors [CAR]
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464411—Immunoglobulin superfamily
    • A61K39/464412—CD19 or B4
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464416—Receptors for cytokines
    • A61K39/464417—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
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464424—CD20
    • 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
    • A61K39/46—Cellular immunotherapy
    • A61K39/464—Cellular immunotherapy characterised by the antigen targeted or presented
    • A61K39/4643—Vertebrate antigens
    • A61K39/4644—Cancer antigens
    • A61K39/464402—Receptors, cell surface antigens or cell surface determinants
    • A61K39/464426—CD38 not IgG
    • 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
    • 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
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • 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
    • 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
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • 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
    • 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
    • C07K14/70596—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
    • C07K16/2803—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
    • C07K16/2887—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
    • 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
    • C07K16/3061—Blood cells
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • 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
    • 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 A61K39/46
    • A61K2239/27—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterized by targeting or presenting multiple antigens
    • A61K2239/29—Multispecific CARs
    • 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 A61K39/46
    • A61K2239/46—Indexing codes associated with cellular immunotherapy of group A61K39/46 characterised by the cancer treated
    • A61K2239/48—Blood cells, e.g. leukemia or lymphoma
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/22—Immunoglobulins specific features characterized by taxonomic origin from camelids, e.g. camel, llama or dromedary
    • 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
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • C07K2317/35—Valency
    • 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
    • C07K2317/565—Complementarity determining region [CDR]
    • 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
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • 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
    • C07K2319/20—Fusion polypeptide containing a tag with affinity for a non-protein ligand
    • C07K2319/21—Fusion polypeptide containing a tag with affinity for a non-protein ligand containing a His-tag
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • 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
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor
    • 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

Abstract

本发明公开了一种基于单域抗体的双特异性嵌合抗原受体及其应用。所述的双特异性单域抗体嵌合抗原受体由CD8信号肽、CD19及CD20抗原特异性的两个单域抗体和CD28跨膜区以及CD28、CD3胞内信号传导结构域依次串联组成。本发明通过优化设计CD19、CD20特异的单域抗体，提供了一种CD19、CD20双靶点修饰的CAR‐T细胞，能够特异地与CD19及CD20抗原结合。在B淋巴细胞系恶性肿瘤杀伤试验中，采用CD19、CD20双靶点修饰的CAR‐T细胞进行CAR‐T疗法与单独的CD19或CD20CAR‐T相比，明显加强了免疫细胞靶向识别肿瘤细胞的能力，也增强了对肿瘤细胞的杀伤活性。

Description

一种基于单域抗体的双特异性嵌合抗原受体及其应用
技术领域
本发明属于生物医学或生物制药技术领域，涉及一种基于单域抗体的双特异性嵌合抗原受体及其应用。
背景技术
随着肿瘤免疫学理论和临床技术的发展，嵌合抗原受体T细胞疗法(Chimericantigen receptor T-cell immunotherapy，CAR-T)成为目前最有发展前景的肿瘤免疫疗法之一。一般，嵌合抗原受体CAR由一个肿瘤相关抗原结合区、胞外铰链区、跨膜区域以及胞内信号转导区组成。CAR-T细胞疗法通过外源基因转染技术，把识别肿瘤相关抗原的单链抗体(Single chain fragment variable，scFv)和T细胞活化序列的融合蛋白表达到T细胞表面，使可以特异识别肿瘤相关抗原的scFv通过跨膜区与T细胞胞内的活化增殖信号域偶联。表达CAR的T细胞以抗原依赖、但非MHC限制的方式结合肿瘤抗原，启动并活化特异性杀伤肿瘤反应。
CD19、CD20分子是治疗B淋巴细胞系肿瘤潜在的靶点，也是CAR研究中的热点。靶向CD19分子的嵌合抗原受体基因修饰的T细胞(CD19 CAR-T)在治疗多发性、难治性的急性B淋巴细胞白血病上取得巨大成功，而在难治性、复发性慢性B淋巴细胞白血病和B淋巴细胞系淋巴瘤的治疗中疗效明显较差。CD20分子也是B淋巴细胞系淋巴瘤，尤其是慢性、套细胞淋巴瘤表面的靶标分子。一般在CD19阳性的B细胞表面都会表达CD20。所以理论上如果能实现针对CD19和CD20的双靶标的双特异性CAR-T技术，其对B淋巴细胞白血病和B淋巴细胞系淋巴瘤的疗效应该可以明显改善。
另外，目前针对CD19的CAR-T细胞疗法在治疗急性B淋巴细胞白血病的临床试验中虽然可以在短期内实现90％左右的完全缓解疗效，但在治疗后数月后发现有约10％的患者发生远期复发，主要原因是残存肿瘤细胞产生了CD19缺失的变异株。因而同时设计针对肿瘤表面CD19及CD20抗原进行协同CAR-T疗法，将不仅有效提高T细胞加强杀伤信号并且可以利用像抗生素联用一样的原理，有效地避免发生靶点逃逸现象引起的远期白血病复发。
CAR-T细胞的有效激活均严重依赖识别肿瘤相关抗原的抗体的特异性以及抗原结合的亲和力高低等性质。所以在目前CAR-T细胞胞内信号转导区的设计已经趋于成熟的现状下，抗原结合区的设计成为新型CAR-T技术开发的重点和关键。从骆驼源重链抗体(Heavychain antibody,HCAb)中克隆出仅由一个重链可变区组成的单链抗体，其大小仅为2.4×4nm，是能够结合抗原的最小片段，称为单域抗体(Variable domain of heavy chain ofheavy-chain antibody,VHH)或纳米抗体。与传统抗体相比，VHH单域抗体分子量小且表达量高，化学稳定性好，亲和力高并且与人源抗体同源性高，免疫原性低。分子量小易于进行基因工程改造，构建双重或多重特异性的单域抗体组合，达到一个分子多靶点或多种功能的效果。VHH组织渗透性好，在进行肿瘤治疗时，具有接触到不能被常规抗体接触的较为隐蔽的靶点的可能性。正由于这些优点，利用单域抗体作为CAR的抗原结合区进行CAR修饰及CAR-T细胞疗法是CAR疗法的创新性的发展。
发明内容
本发明的目的是针对现有技术的上述不足，提供一种应用于高效拮抗包括血液病在内的各种癌症的多靶点的CAR-T细胞疗法中的双特异性单域抗体嵌合抗原受体。
本发明的另一目的是提供含有该双特异性单域抗体嵌合抗原受体的T淋巴细胞或其他免疫效应细胞。
本发明的又一目的是提供该双特异性单域抗体嵌合抗原受体的应用。
本发明的目的可通过以下技术方案实现：一种基于单域抗体的双特异性嵌合抗原受体，胞外信号肽，由两个不同单域抗体构成的抗原结合结构域，跨膜结构域和胞内信号传导结构域共同组成。
所述基于单域抗体的双特异性嵌合抗原受体,其抗原与恶性肿瘤相关联，可以选自CD19、CD20、CD22、CD33/IL3Rα、CD38、BCMA、CS1、CD138、c-Met、EGFRvIII、GD-2、NY-ESO-1、MAGE A3、糖脂F77中任意二者的组合；优选CD19与CD20的组合；进一步优选的包括CD19及CD20抗原特异性的两个单域抗体VHH链组成的抗原结合结构域，并由一个Linker连接。
其中，所述的CD19抗原特异性的单域抗体VHH链包括框架区FR和互补决定区CDR，所述框架区FR包括FR1～FR4的氨基酸序列：SEQ ID NO:4所示的FR1，SEQ ID NO:5所示的FR2，SEQ ID NO:6所示的FR3，SEQ ID NO:7所示的FR4；所述互补决定区CDR包括CDR1～CDR3的氨基酸序列：SEQ ID NO:8所示的CDR1，SEQ ID NO:9所示的CDR2，SEQ ID NO:10所示的CDR3。
所述的CD19抗原特异性的单域抗体VHH链优选具有SEQ ID NO:3所示的氨基酸序列。
编码所述的CD19抗原特异性的单域抗体VHH链的核苷酸序列优选如SEQ ID NO:11所示。
所述的CD20抗原特异性的单域抗体VHH链包括框架区FR和互补决定区CDR，所述框架区FR包括FR1～FR4的氨基酸序列：SEQ ID NO:13所示的FR1，SEQ ID NO:14所示的FR2，SEQ ID NO:15所示的FR3，SEQ ID NO:16所示的FR4；所述互补决定区CDR包括CDR1～CDR3的氨基酸序列：SEQ ID NO:17所示的CDR1，SEQ ID NO:18所示的CDR2，SEQ ID NO:19所示的CDR3。
所述的CD20抗原特异性的单域抗体VHH链优选具有SEQ ID NO:12所示的氨基酸序列。
编码所述的CD20抗原特异性的单域抗体VHH链的核苷酸序列如SEQ ID NO:20所示。
所述基于单域抗体的双特异性嵌合抗原受体优选进一步包括共刺激信号传导区，包括选自下列的共刺激分子的细胞内结构域：CD27、CD28、4-1BB、OX40、CD30、CD40、CD3、淋巴细胞功能相关抗原-1(LFA-1)、CD2、CD7、LIGHT、NKG2C、B7-H3与CD83特异性结合的配体和其任意组合。
所述基于单域抗体的双特异性嵌合抗原受体优选地由CD8信号肽、CD19及CD20抗原特异性的两个单域抗体、CD28跨膜区以及CD28、CD3胞内信号传导结构域依次串联组成。
所述基于单域抗体的双特异性嵌合抗原受体更进一步优选具有SEQ ID NO:1所示的氨基酸序列，其编码基因序列如SEQ ID NO:2所示。
一种基因工程改造的免疫效应细胞，包括编码本发明所述的双特异性嵌合抗原受体的核苷酸序列。所述的免疫效应细胞选自T淋巴细胞、NK细胞，造血干细胞、多能干细胞或胚胎干细胞培养分化的免疫细胞，优选T淋巴细胞。
其中，所述嵌合抗原受体优选由CD8信号肽、CD19及CD20抗原特异性的两个单域抗体、CD28跨膜区以及CD28、CD3胞内信号传导结构域依次串联组成。
所述嵌合抗原受体进一步优选具有SEQ ID NO:1所示的氨基酸序列，其编码基因序列如SEQ ID NO:2所示。
本发明所述的双特异性嵌合抗原受体在制备抗肿瘤药物中的应用；优选在制备抗血液恶性肿瘤的药物中的应用。
本发明所述的免疫效应细胞在制备抗肿瘤药物中的应用；优选在制备抗血液恶性肿瘤的药物中的应用。
有益效果：
我们利用基因工程手段设计双特异性单域抗体作为CAR的抗原结合区进行CAR修饰及CAR-T细胞疗法是CAR疗法的创新性的发展。例如，将两个单域抗体结合起来(两个重链串联)蛋白质结构上和一个重链与轻链串联的scFv其实非常相似，我们的研究也证实双特异性单域抗体完全可以作为CAR技术的抗原结合域使用，从而成功地实现了双靶点双特异性的CAR技术，也在疗效试验中验证了前述双特异性CAR技术相对于传统CAR-T技术的多种理论优势。同时我们发现此发明还得以避免了以scFv为基础设计的CAR-T所常有的表达困难、稳定性差等缺陷。我们的CD19x CD20双特异性单域抗体-CAR技术在体外高效地转导了健康人T淋巴细胞，对于CD19和CD20阳性的靶细胞产生了强力的杀伤效果，在基于NOG小鼠的高质量人淋巴瘤模式动物体内起到了比单特异性CAR-T更好的治疗效果。
本发明通过优化设计CD19、CD20特异的单域抗体，提供了一种CD19、CD20双靶点修饰的CAR-T细胞，能够特异地与CD19及CD20抗原结合。此外，在B淋巴细胞系恶性肿瘤治疗中，采用CD19、CD20双靶点修饰的CAR-T细胞进行CAR-T疗法与单独的CD19或CD20CAR-T相比，明显增强了免疫细胞靶向识别肿瘤抗原的能力，加强了对肿瘤细胞的杀伤活性。
附图说明
图1为基于CD19xCD20单域抗体的嵌合抗原受体结构图。
图2为基于CD19xCD20单域抗体双特异性CAR-T体外杀伤效果图。其中，Raji细胞为靶细胞，A)只加入未转导的T细胞，B)加入CD19 CAR-T细胞，C)加入CD19 CAR-T细胞，D)加入CD19xCD20 CAR-T细胞。根据Raji细胞占总细胞的比例结果显示，与未加入CAR-T细胞的对照组相比，B)、C)与D)组对Raji肿瘤细胞均有杀伤作用，而CD19xCD20 CAR-T细胞的杀伤效果最好。
图3为小鼠生存曲线；分别对24只NOG小鼠尾静脉注射Raji细胞。10天以后，将注射Raji细胞的小鼠随机分成四组，分别注射等量(400万细胞)的T细胞、CD19 CAR-T细胞、CD20CAR-T细胞以及CD19xCD20 CAR-T细胞。连续观察动物5周，记录小鼠死亡时间。注射未转导T细胞的小鼠基本上在20天内全部死亡，注射CD19 CAR-T细胞的小鼠在40天时发生1例死亡，注射CD20 CAR-T细胞的小鼠在42天时发生1例死亡，而注射CD19xCD20 CAR-T细胞的小鼠在观察期间均未发生死亡。
具体实施方式
本发明利用多个各自特异的单域抗体进行CAR设计修饰，涉及识别多个靶点的CAR-T技术，协同杀伤包括血液系肿瘤的肿瘤，防止免疫逃逸及肿瘤复发。下面结合具体实施例，进一步阐述本发明。
实施例1 CD19与CD20单域抗体制备
(一)CD19与CD20单域抗体文库构建
利用购自R&D SYSTEMS公司的CD19及CD20抗原对美洲驼进行定期免疫。第一次免疫时，分别将200μg重组CD19或CD20蛋白与等体积弗氏佐剂混合，其后用弗氏不完全佐剂与抗原混合，进行免疫，每周一次。经多次免疫加强美洲驼对靶抗原的免疫应激反应，刺激B细胞表达针对靶抗原的重链抗体。
免疫期间对免疫动物取血采样，评估免疫反应效果。免疫结束后，取100mL美洲驼外周血淋巴细胞并提取Total RNA，并反转录成cDNA，通过二次PCR扩增美洲驼重链抗体的可变区片段VHH。将VHH片段构建入噬菌体展示载体中，并通过电转化将携带有单域抗体基因片段的产物转入感受态大肠杆菌中，从而获得单域抗体免疫文库。
第一次PCR模板：cDNA；
上游引物CALL001，如SEQ ID NO:21所示：5’-GTCCTGGCTGCTCTTCTACAAGG-3’；
下游引物CALLOO2，如SEQ ID NO:22所示：5’-GGTACGTGCTGTTGAACTGTTCC-3’；
第二次PCR模板：第一次PCR割胶回收产物；
上游引物BACK-1，如SEQ ID NO:23所示：5’-GATGTGCAGCTGCAGGAGTCTGGAGGAGG-3’；BACK-2，如SEQ ID NO:24所示：5’-GATGTGCAGCTGCAGGAGTCTGGGGGAGG-3’；
下游引物PMCF，如SEQ ID NO:25所示：5’-CTAGTGCGGCCGCTGAGGAGACGGTGACCTGGGT-3’；
两次PCR程序均为：预变性94℃、7min，变性94℃、1min，退火55℃、1min，延伸72℃、7min。
(二)CD19与CD20单域抗体筛选及表达
利用噬菌体展示技术将单域抗体分子展示于噬菌体表面，进而筛选出抗原特异性的单域抗体。通过噬菌体酶联免疫吸附ELISA方法，将抗原用100mM NaHCO3(pH 8.0)稀释至终浓度为100μg/mL,包被100μL至96孔板中，4℃过夜。经过PBS冲洗、1％脱脂牛奶封闭后，加入噬菌体孵育1～2h，然后将抗原特异性的噬菌体洗脱并侵染TG1细胞，在含有氨苄青霉素的LB培养板上涂布培养，经过多轮筛选逐步达到富集。挑选大量阳性克隆进行ELISA检测并对阳性克隆进行测序，根据序列比对，确定独特的的克隆并将其序列分为框架区FR和互补决定区CDR。
将测序正确的克隆接种在5mL含有氨苄青霉素的LB培养液中，37℃摇床培养过夜；接种1mL的菌液至300mL TB培养液中，37℃摇床培养至OD600nm＝0.6～0.9时，加入1M IPTG，28℃摇床培养过夜；离心，收菌；利用渗透法，获得抗体粗提液；通过Protein L标记并利用亲和层析法纯化出单域抗体，其产量均在10mg/L以上。利用SPR技术检测抗体的亲和力，进一步筛选出特异性高的单域抗体。通过以上实施方式，共获得6株CD19单域抗体、5株CD20单域抗体。选择亲和力较高的单域抗体，其中一株CD19单域抗体具有SEQ ID NO:11所示的核甘酸序列，一株CD20单域抗体具有SEQ ID NO:20所示的核甘酸序列。
实施例2 CD19与CD20双特异性嵌合抗原受体修饰的T细胞的制备
(一)嵌合抗原受体基因片段制备
本发明按以下编码基因的顺序设计融合基因片段：CD8信号肽、CD19 VHH-linker-CD20 VHH、CD28跨膜区以及CD28和CD3ζ胞内信号结构域，通过基因合成技术直接合成该融合基因，使表达的嵌合抗原受体具有CD8α-VHH(CD19-linker-CD20)-CD28 TM-CD28-CD3ζ的氨基酸结构。将购自Clontech公司的pLVX-Puro载体的CMV启动子改造为人EF1a启动子从而获得pLVX-hEF1α载体，将合成的基因片段构建在pLVX-hEF1α载体上，形成重组质粒，命名为pLVX-CD8α-VHH(CD19-linker-CD20)-CD28 TM-CD28-CD3ζ。
CD8信号肽的核酸序列如SEQ ID NO:26所示；
Linker的核酸序列如SEQ ID NO:27所示；
CD28 TM及CD28-CD3ζ胞内信号结构域的核酸序列如SEQ ID NO:28所示；
(二)嵌合抗原受体慢病毒表达载体的构建
在本发明中，CAR-T细胞通过基因修饰的CAR、慢病毒表达载体构建，转导T细胞而获得。提取pLVX-CD8α-VHH(CD19-linker-CD20)-CD28 TM-CD28-CD3ζ表达质粒和pRRE、pRSV-rev及pMD2.G辅助质粒，按一定比例混合，共转染293T细胞。转染48h、96h后，收集含有病毒的细胞培养上清，4℃、3000rpm离心5min。上清经0.45μm滤器过滤后，与PEG8000/NaCl按4:1体积混匀，4℃静置2～3h后高速离心30min。弃上清，沉淀用预冷的PBS重悬溶解，即获得病毒浓缩液，-80℃保存备用。
(三)T淋巴细胞的制备
取50mL健康人新鲜血液，通过淋巴细胞分离液、密度梯度离心方法分离外周血单核细胞(PBMC)。利用Pan T Cell Isolation Kit(购自Miltenyi Biotech)对细胞进行磁珠标记，并分离纯化出T淋巴细胞。纯化后的T细胞，再利用CD3/CD28磁珠进行T淋巴细胞激活及增殖。
(四)慢病毒转导T淋巴细胞
收集激活的T淋巴细胞，重悬在含有终浓度为100IU/mL IL-2的R10培养基中。用相同培养基将慢病毒稀释至MOI＝5，感染1x106个活化的T淋巴细胞，并加入终浓度为7μg/mL的聚凝胺，32℃、1000g离心1h。将细胞悬液加在24孔板中，置37℃、5％CO2培养箱中孵育过夜。第二天，再次离心并换新鲜培养基，每隔2天检测一次细胞浓度。当细胞浓度达到2x106个/mL时，离心吸取1mL细胞悬液到另一个孔中，并分别加入新鲜培养基，继续扩大培养。
实施例3 CD19与CD20双特异性CAR-T细胞对肿瘤的杀伤试验
(一)体外杀伤试验
离心收集实施例2中制备的CD19xCD20 CAR-T细胞，用含10％人AB血清的DPBS调节浓度，洗涤三次后接种在96孔板中，用Protein L进行标记。Raji肿瘤细胞用Calcein-AM标记，标记后的CAR-T与肿瘤细胞按1:1、5:1、10:1及20:1比率在37℃条件下共培养4h，利用流式细胞技术FACS进行检测。每种细胞设置三个阴性对照，分别为只加CD19 CAR-T或CD20CAR-T及非CAR修饰的T细胞的肿瘤细胞。试验结果显示与未注射CAR-T细胞的对照组相比，B)、C)与D)组对Raji肿瘤细胞均有杀伤作用，而CD19xCD20 CAR-T细胞的杀伤效果最好。
(二)动物模型试验
扩增Raji细胞，按4x106细胞量/只小鼠，分别进行24只高度免疫缺陷NOG小鼠尾静脉注射，建立模型。10天后将注射Raji细胞的小鼠分成四组，每组6只，分别注射等量的Tcell、CD19 CAR-T cell、CD20 CAR-T cell、CD19xCD20 CAR-T cell。连续饲养5周，观察小鼠状态，若有小鼠死亡，及时记录死亡时间，绘制小鼠生存曲线。小鼠模型试验表明，注射T细胞的小鼠基本上在20天内死亡，注射单一CD19 CAR-T cell或CD20 CAR-T cell的小鼠有少量死亡，而注射CD19xCD20 CAR-T细胞的小鼠均未发生死亡，说明本发明设计的CD19xCD20 CAR-T细胞在模式动物体内同样对肿瘤细胞具有杀伤作用。

Claims (7)

1.一种基于单域抗体的双特异性嵌合抗原受体，其特征在于包括胞外信号肽，由两个不同单域抗体构成的抗原结合结构域，跨膜结构域和胞内信号传导结构域;所述嵌合抗原受体具有SEQ ID NO: 1所示的氨基酸序列，其编码基因序列如SEQ ID NO: 2所示。
2.一种基因工程改造的免疫效应细胞，其特征在于包括编码权利要求1所述的双特异性嵌合抗原受体的核苷酸序列；所述的免疫效应细胞选自T淋巴细胞、NK细胞，多能干细胞或胚胎干细胞培养分化的免疫细胞。
3.根据权利要求2所述的基因工程改造的免疫效应细胞，其特征在于所述的免疫效应细胞为T淋巴细胞。
4.权利要求1所述基于单域抗体的双特异性嵌合抗原受体在制备抗肿瘤药物中的应用。
5.根据权利要求4所述的应用，其特征在于权利要求1所述基于单域抗体的双特异性嵌合抗原受体在制备抗血液恶性肿瘤的药物中的应用。
6.权利要求2所述的免疫效应细胞在制备抗肿瘤药物中的应用。
7.根据权利要求6所述的应用，其特征在于权利要求2所述的免疫效应细胞在制备抗恶性肿瘤的药物中的应用。
CN201510733585.2A 2015-08-11 2015-11-02 一种基于单域抗体的双特异性嵌合抗原受体及其应用 Active CN105384825B (zh)

Priority Applications (33)

Application Number Priority Date Filing Date Title
CN201510733585.2A CN105384825B (zh) 2015-08-11 2015-11-02 一种基于单域抗体的双特异性嵌合抗原受体及其应用
EA201890302A EA201890302A1 (ru) 2015-08-11 2016-08-10 Химерные рецепторы антигенов на основе однодоменных антител и способы их применения
AU2016305075A AU2016305075B2 (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
CR20180153A CR20180153A (es) 2015-08-11 2016-08-10 Receptores de antígenes quiméricos basados en anticuerpos de dominio simple y métodos de uso de estos
CA2994579A CA2994579C (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
PCT/CN2016/094408 WO2017025038A1 (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
US15/751,609 US10934363B2 (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single domain antibodies and methods of use thereof
SG10201913485QA SG10201913485QA (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
IL257297A IL257297B (en) 2015-08-11 2016-08-10 Chimeric Antigen Receptors Based on Single-Site Antibodies and Methods for Using Them
KR1020187006996A KR20180035918A (ko) 2015-08-11 2016-08-10 단일-도메인 항체에 근거된 키메라 항원 수용체 및 이들의 이용 방법
NZ758571A NZ758571A (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
IL294683A IL294683A (en) 2015-08-11 2016-08-10 Chimeric Antigen Receptors Based on Single-Site Antibodies and Methods for Using Them
BR112018002844-4A BR112018002844A2 (pt) 2015-08-11 2016-08-10 receptores de antígeno quimérico à base de anticorpos de domínio único e métodos de uso dos mesmos
JP2018526984A JP6859347B2 (ja) 2015-08-11 2016-08-10 単一ドメイン抗体に基づくキメラ抗原受容体及びその使用方法
EP16834662.5A EP3334765A4 (en) 2015-08-11 2016-08-10 CHIMERIC ANTIGEN RECEPTORS BASED ON INDIVIDUAL DOMAIN ANTIBODIES AND METHOD FOR USE THEREOF
MYPI2018000199A MY188362A (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
CR20210225A CR20210225A (es) 2015-08-11 2016-08-10 RECEPTORES DE ANTÍGENES QUIMÉRICOS BASADOS EN ANTICUERPOS DE DOMINIO SIMPLE Y MÉTODOS DE USO DE ESTOS (Divisional 2018-0153)
MX2018001739A MX2018001739A (es) 2015-08-11 2016-08-10 Receptores de antígenos quiméricos basados en anticuerpos de dominio simple y métodos de uso de estos.
EP22168161.2A EP4063397A1 (en) 2015-08-11 2016-08-10 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
UAA201802367A UA125818C2 (uk) 2015-08-11 2016-08-10 Химерні рецептори антигенів на основі однодоменних антитіл і способи їх застосування
ZA2018/00703A ZA201800703B (en) 2015-08-11 2018-02-02 Chimeric antigen receptors based on single¿domain antibodies and methods of use thereof
CL2018000378A CL2018000378A1 (es) 2015-08-11 2018-02-09 Receptores de antígenos quiméricos basados en anticuerpos de dominio simple y métodos de uso de estos
MX2022015823A MX2022015823A (es) 2015-08-11 2018-02-09 Receptores de antigenos quimerlcos basados en anticuerpos de dominio simple y metodos de uso de estos.
PH12018500295A PH12018500295A1 (en) 2015-08-11 2018-02-09 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
SA518390904A SA518390904B1 (ar) 2015-08-11 2018-02-11 مستقبلات مولد مضاد خيمرية تقوم على أجسام مضادة أحادية الحقل وطرق لاستخدامها
CONC2018/0001405A CO2018001405A2 (es) 2015-08-11 2018-02-13 Receptores de antígenos quiméricos basados en anticuerpos de dominio simple
AU2020200151A AU2020200151C1 (en) 2015-08-11 2020-01-08 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
US17/164,125 US20210261675A1 (en) 2015-08-11 2021-02-01 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
JP2021052453A JP7168173B2 (ja) 2015-08-11 2021-03-25 単一ドメイン抗体に基づくキメラ抗原受容体及びその使用方法
CL2021001686A CL2021001686A1 (es) 2015-08-11 2021-06-23 Receptores de antígenos quiméricos basados en anticuerpos de dominio simple y métodos de uso de estos (divisional de solicitud n° 201800378)
AU2022204180A AU2022204180A1 (en) 2015-08-11 2022-06-15 Chimeric antigen receptors based on single-domain antibodies and methods of use thereof
JP2022167222A JP2022183283A (ja) 2015-08-11 2022-10-18 単一ドメイン抗体に基づくキメラ抗原受容体及びその使用方法
JP2024014929A JP2024032975A (ja) 2015-08-11 2024-02-02 単一ドメイン抗体に基づくキメラ抗原受容体及びその使用方法

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CN201510490002 2015-08-11
CN2015104900028 2015-08-11
CN201510733585.2A CN105384825B (zh) 2015-08-11 2015-11-02 一种基于单域抗体的双特异性嵌合抗原受体及其应用

Publications (2)

Publication Number Publication Date
CN105384825A CN105384825A (zh) 2016-03-09
CN105384825B true CN105384825B (zh) 2018-06-01

Family

ID=55417644

Family Applications (8)

Application Number Title Priority Date Filing Date
CN201510733585.2A Active CN105384825B (zh) 2015-08-11 2015-11-02 一种基于单域抗体的双特异性嵌合抗原受体及其应用
CN201680047777.0A Pending CN109311999A (zh) 2015-08-11 2016-08-10 基于单结构域抗体的嵌合抗原受体及其使用方法
CN202110530320.8A Active CN113234173B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110530335.4A Active CN113234174B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN201780031233.XA Active CN109153731B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202410006229.XA Pending CN117756941A (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110529747.6A Pending CN113185615A (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110529749.5A Active CN113185616B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法

Family Applications After (7)

Application Number Title Priority Date Filing Date
CN201680047777.0A Pending CN109311999A (zh) 2015-08-11 2016-08-10 基于单结构域抗体的嵌合抗原受体及其使用方法
CN202110530320.8A Active CN113234173B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110530335.4A Active CN113234174B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN201780031233.XA Active CN109153731B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202410006229.XA Pending CN117756941A (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110529747.6A Pending CN113185615A (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法
CN202110529749.5A Active CN113185616B (zh) 2015-08-11 2017-08-10 靶向bcma的嵌合抗原受体及其使用方法

Country Status (30)

Country Link
US (5) US10934363B2 (zh)
EP (6) EP3334765A4 (zh)
JP (7) JP6859347B2 (zh)
KR (5) KR20180035918A (zh)
CN (8) CN105384825B (zh)
AU (5) AU2016305075B2 (zh)
BR (2) BR112018002844A2 (zh)
CA (3) CA2994579C (zh)
CL (4) CL2018000378A1 (zh)
CO (2) CO2018001405A2 (zh)
CR (4) CR20180153A (zh)
DK (1) DK3896091T3 (zh)
EA (2) EA201890302A1 (zh)
FI (1) FI3896091T3 (zh)
HR (1) HRP20231542T1 (zh)
HU (1) HUE064534T2 (zh)
IL (3) IL294683A (zh)
LT (1) LT3896091T (zh)
MX (3) MX2018001739A (zh)
MY (2) MY188362A (zh)
NZ (1) NZ750366A (zh)
PH (2) PH12018500295A1 (zh)
PT (1) PT3896091T (zh)
RS (1) RS64925B1 (zh)
SA (1) SA518390904B1 (zh)
SG (2) SG10201913485QA (zh)
SI (1) SI3896091T1 (zh)
UA (2) UA125818C2 (zh)
WO (2) WO2017025038A1 (zh)
ZA (2) ZA201800703B (zh)

Families Citing this family (290)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10704021B2 (en) 2012-03-15 2020-07-07 Flodesign Sonics, Inc. Acoustic perfusion devices
US10967298B2 (en) 2012-03-15 2021-04-06 Flodesign Sonics, Inc. Driver and control for variable impedence load
US9950282B2 (en) 2012-03-15 2018-04-24 Flodesign Sonics, Inc. Electronic configuration and control for acoustic standing wave generation
US9458450B2 (en) 2012-03-15 2016-10-04 Flodesign Sonics, Inc. Acoustophoretic separation technology using multi-dimensional standing waves
US9725710B2 (en) 2014-01-08 2017-08-08 Flodesign Sonics, Inc. Acoustophoresis device with dual acoustophoretic chamber
CN104004095B (zh) * 2014-06-04 2016-11-23 博生吉医药科技(苏州)有限公司 一种cd7纳米抗体、其编码序列及应用
US11708572B2 (en) 2015-04-29 2023-07-25 Flodesign Sonics, Inc. Acoustic cell separation techniques and processes
US11377651B2 (en) 2016-10-19 2022-07-05 Flodesign Sonics, Inc. Cell therapy processes utilizing acoustophoresis
US11021699B2 (en) 2015-04-29 2021-06-01 FioDesign Sonics, Inc. Separation using angled acoustic waves
JP6961497B2 (ja) * 2015-06-25 2021-11-05 アイセル・ジーン・セラピューティクス・エルエルシー キメラ抗体受容体（ＣＡＲｓ）の構成およびその使用方法
US11459540B2 (en) 2015-07-28 2022-10-04 Flodesign Sonics, Inc. Expanded bed affinity selection
US11474085B2 (en) 2015-07-28 2022-10-18 Flodesign Sonics, Inc. Expanded bed affinity selection
CN105384825B (zh) * 2015-08-11 2018-06-01 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
WO2017122018A1 (en) 2016-01-12 2017-07-20 Crescendo Biologics Limited Molecules that bind prostate specific membrane antigen (psma)
SG10202007836WA (en) 2016-02-17 2020-09-29 Seattle Genetics Inc Bcma antibodies and use of same to treat cancer and immunological disorders
CN110699371A (zh) * 2016-03-18 2020-01-17 江苏普瑞康生物医药科技有限公司 一种基于FcγRⅢa的嵌合基因及其用途
KR102522622B1 (ko) 2016-04-01 2023-04-18 카이트 파마 인코포레이티드 Bcma 결합 분자 및 그의 사용 방법
AR108427A1 (es) * 2016-04-01 2018-08-22 Kite Pharma Inc Antígeno quimérico y receptores de células t y métodos de uso
US11214789B2 (en) 2016-05-03 2022-01-04 Flodesign Sonics, Inc. Concentration and washing of particles with acoustics
US11085035B2 (en) 2016-05-03 2021-08-10 Flodesign Sonics, Inc. Therapeutic cell washing, concentration, and separation utilizing acoustophoresis
GB201607968D0 (en) 2016-05-06 2016-06-22 Crescendo Biolog Ltd Chimeric antigen receptor
US11623958B2 (en) 2016-05-20 2023-04-11 Harpoon Therapeutics, Inc. Single chain variable fragment CD3 binding proteins
US10100106B2 (en) 2016-05-20 2018-10-16 Harpoon Therapeutics, Inc. Single domain serum albumin binding protein
KR20230129583A (ko) 2016-06-21 2023-09-08 테네오바이오, 인코포레이티드 Cd3 결합 항체
KR20190063458A (ko) * 2016-07-15 2019-06-07 포세이다 테라퓨틱스, 인크. Ｍｕｃ1에 특이적인 키메라 항원 수용체(ｃａｒｓ) 및 그의 사용 방법
EP4050034A1 (en) 2016-09-14 2022-08-31 TeneoOne, Inc. Cd3 binding antibodies
WO2018058432A1 (zh) * 2016-09-28 2018-04-05 李华顺 一种多基因重组嵌合抗原受体分子及其应用
WO2018068201A1 (en) * 2016-10-11 2018-04-19 Nanjing Legend Biotech Co., Ltd. Single-domain antibodies and variants thereof against ctla-4
EP3529347A1 (en) 2016-10-19 2019-08-28 Flodesign Sonics, Inc. Affinity cell extraction by acoustics
CN106755108A (zh) * 2016-12-05 2017-05-31 刘晓明 一种表达cd19和cd20抗体基因嵌合抗原受体的慢病毒载体及其制备方法
CN106701827A (zh) * 2016-12-05 2017-05-24 刘晓明 表达cd19和cd20抗体基因嵌合抗原受体t细胞的转化及扩增培养与保存方法
CN106755109A (zh) * 2016-12-05 2017-05-31 刘晓明 一种表达人cd19和cd20嵌合抗原受体基因的慢病毒载体
KR20190114966A (ko) 2016-12-09 2019-10-10 온키뮨 리미티드 조작된 자연 살해 세포 및 이의 용도
CN106822184A (zh) * 2016-12-15 2017-06-13 梁爱斌 多靶点联合的car‑t细胞制剂与制备方法
BR112019012354A2 (pt) * 2016-12-21 2019-11-26 Teneobio Inc anticorpos apenas de cadeia pesada anti-bcma
CN108276493B (zh) * 2016-12-30 2023-11-14 南京传奇生物科技有限公司 一种嵌合抗原受体及其应用
CN106749677B (zh) * 2017-01-04 2020-06-12 上海交通大学医学院附属瑞金医院 一种靶向mll白血病的双特异性嵌合抗原受体基因及其应用
EP3565840A1 (en) 2017-01-06 2019-11-13 Crescendo Biologics Limited Single domain antibodies to programmed cell death (pd-1)
US20190375815A1 (en) 2017-01-31 2019-12-12 Novartis Ag Treatment of cancer using chimeric t cell receptor proteins having multiple specificities
CN108395482B (zh) * 2017-02-08 2021-02-05 西比曼生物科技（香港）有限公司 一种靶向cd20抗原嵌合抗原受体的构建及其工程化t细胞的活性鉴定
CA3052779A1 (en) 2017-02-17 2018-08-23 Fred Hutchinson Cancer Research Center Combination therapies for treatment of bcma-related cancers and autoimmune disorders
WO2018160754A2 (en) 2017-02-28 2018-09-07 Harpoon Therapeutics, Inc. Inducible monovalent antigen binding protein
JP7164544B2 (ja) 2017-04-11 2022-11-01 インヒブルクス インコーポレイテッド 制約されたｃｄ３結合を有する多重特異性ポリペプチド構築物およびそれを使用する方法
CN108728465A (zh) * 2017-04-14 2018-11-02 深圳新诺微环生物科技有限公司 一种表达靶细胞-效应细胞桥接器的微环dna载体及其制备方法和应用
IL310182A (en) * 2017-04-26 2024-03-01 Eureka Therapeutics Inc ׂ A Delaware Corp Structures of chimeric antibody/T-cell receptor and uses thereof
WO2018201056A1 (en) 2017-04-28 2018-11-01 Novartis Ag Cells expressing a bcma-targeting chimeric antigen receptor, and combination therapy with a gamma secretase inhibitor
US20200179511A1 (en) 2017-04-28 2020-06-11 Novartis Ag Bcma-targeting agent, and combination therapy with a gamma secretase inhibitor
BR112019022893A2 (pt) 2017-05-01 2020-05-19 Juno Therapeutics Inc combinação de uma terapia celular e um composto imunomodulatório
SG10202107880XA (en) 2017-05-12 2021-09-29 Harpoon Therapeutics Inc Mesothelin binding proteins
CN107299110B (zh) * 2017-05-27 2019-11-22 上海优卡迪生物医药科技有限公司 一种基于octs技术的胰腺癌、恶性间皮瘤car-t治疗载体及其构建方法和应用
CN107245500B (zh) * 2017-05-27 2019-05-17 上海优卡迪生物医药科技有限公司 一种基于octs技术的淋系白血病car-t治疗载体及其构建方法和应用
CN107337736B (zh) * 2017-06-06 2019-07-26 上海优卡迪生物医药科技有限公司 Octs-car双靶向嵌合抗原受体、编码基因、重组表达载体及其构建和应用
US11897953B2 (en) 2017-06-14 2024-02-13 The Broad Institute, Inc. Compositions and methods targeting complement component 3 for inhibiting tumor growth
CA3067584A1 (en) * 2017-06-20 2018-12-27 Teneobio, Inc. Anti-bcma heavy chain-only antibodies
AU2018288803A1 (en) 2017-06-20 2020-02-06 Teneoone, Inc. Anti-BCMA heavy chain-only antibodies
WO2019000223A1 (en) * 2017-06-27 2019-01-03 Nanjing Legend Biotech Co., Ltd. ENABLERS OF IMMUNE EFFECTOR CELLS OF CHIMERIC ANTIBODIES AND METHODS OF USE THEREOF
ES2928296T3 (es) * 2017-06-30 2022-11-16 Us Health Receptores de antígenos quiméricos anti-antígenos de maduración de linfocitos B con dominios humanos
GB201711068D0 (en) 2017-07-10 2017-08-23 Crescendo Biologics Ltd Therapeutic molecules binding PSMA
CN109232742B (zh) * 2017-07-11 2021-10-22 深圳市第二人民医院 一种嵌合抗原受体及其应用
US20200165348A1 (en) * 2017-07-20 2020-05-28 H. Lee Moffitt Cancer Center And Research Institute, Inc. Cd123-binding chimeric antigen receptors
CN109996872A (zh) * 2017-07-20 2019-07-09 深圳普瑞金生物药业有限公司 一种用于***的egfr单域抗体cart及其应用
CA3071624A1 (en) 2017-07-31 2019-02-07 Lentigen Technology, Inc. Compositions and methods for treating cancer with anti-cd19/cd20 immunotherapy
SG11202002093TA (en) * 2017-09-13 2020-04-29 Teneobio Inc Heavy chain antibodies binding to ectoenzymes
KR102403046B1 (ko) 2017-09-29 2022-05-30 재단법인 목암생명과학연구소 Bcma에 높은 친화도를 가지는 항-bcma 항체 및 이를 포함하는 암 치료용 약학적 조성물
EP3694871A4 (en) * 2017-10-13 2021-11-10 Harpoon Therapeutics, Inc. B-CELL MATURATION ANTIG-BINDING PROTEINS
WO2019075359A1 (en) * 2017-10-13 2019-04-18 Harpoon Therapeutics, Inc. TRISPECIFIC PROTEINS AND METHODS OF USE
JP2021501570A (ja) 2017-10-18 2021-01-21 ノバルティス アーゲー 選択的タンパク質分解のための組成物及び方法
KR20200116077A (ko) 2017-11-01 2020-10-08 주노 쎄러퓨티크스 인코퍼레이티드 B 세포 성숙 항원에 특이적인 키메라 항원 수용체 및 암호화 폴리뉴클레오타이드
AU2018359907A1 (en) 2017-11-06 2020-05-07 Fred Hutchinson Cancer Center Combination of a cell therapy and a gamma secretase inhibitor
WO2019094983A1 (en) 2017-11-13 2019-05-16 The Broad Institute, Inc. Methods and compositions for treating cancer by targeting the clec2d-klrb1 pathway
WO2019099639A1 (en) 2017-11-15 2019-05-23 Navartis Ag Bcma-targeting chimeric antigen receptor, cd19-targeting chimeric antigen receptor, and combination therapies
MX2020005651A (es) 2017-11-30 2020-10-28 Novartis Ag Receptor de antigeno quimerico dirigido a bcma y usos del mismo.
EP3725092A4 (en) 2017-12-14 2021-09-22 FloDesign Sonics, Inc. DRIVE AND CONTROL UNIT FOR ACOUSTIC CONVERTER
CA3084553A1 (en) * 2017-12-22 2019-06-27 Bluebird Bio, Inc. Multivalent chimeric antigen receptor
CN109970860A (zh) * 2017-12-27 2019-07-05 信达生物制药(苏州)有限公司 三链抗体、其制备方法及其用途
CN109971715A (zh) * 2017-12-28 2019-07-05 深圳华大生命科学研究院 一种扩增特异性car-t细胞的培养方法
WO2019127215A1 (en) * 2017-12-28 2019-07-04 Nanjing Legend Biotech Co., Ltd. Multispecific chimeric receptors comprising an nkg2d domain and methods of use thereof
CN109988242A (zh) * 2018-01-02 2019-07-09 武汉波睿达生物科技有限公司 联合嵌合抗原受体、表达载体、慢病毒及t细胞
EP3737408A1 (en) 2018-01-08 2020-11-18 Novartis AG Immune-enhancing rnas for combination with chimeric antigen receptor therapy
CN108285486A (zh) * 2018-01-15 2018-07-17 浙江阿思科力生物科技有限公司 以cd20为靶点的特异性抗体、car-nk细胞及其制备和应用
KR102115236B1 (ko) * 2018-01-29 2020-05-27 (주)에스엠티바이오 췌장 또는 담관계암 치료를 위한 키메라 항원 수용체
CN108341881B (zh) * 2018-01-31 2020-08-18 深圳市默赛尔生物医学科技发展有限公司 带安全开关的嵌合抗原受体及其表达基因、其修饰的nk细胞及应用
WO2019152660A1 (en) 2018-01-31 2019-08-08 Novartis Ag Combination therapy using a chimeric antigen receptor
CN108314739B (zh) * 2018-02-05 2020-07-14 深圳市默赛尔生物医学科技发展有限公司 多信号嵌合抗原受体及其表达基因、其修饰的nk细胞及应用
CN110129369B (zh) * 2018-02-09 2023-10-13 上海交通大学医学院附属上海儿童医学中心 一种嵌合抗原受体基因工程载体、免疫细胞及其应用
EP3752203A1 (en) 2018-02-13 2020-12-23 Novartis AG Chimeric antigen receptor therapy in combination with il-15r and il15
GB201802573D0 (en) 2018-02-16 2018-04-04 Crescendo Biologics Ltd Therapeutic molecules that bind to LAG3
EP3759146A1 (en) 2018-03-02 2021-01-06 CDR-Life AG Trispecific antigen binding proteins
CN108220247A (zh) * 2018-03-20 2018-06-29 杭州史迪姆生物科技有限公司 一种双car-t细胞及其制备方法和应用
US20210023138A1 (en) * 2018-04-06 2021-01-28 The Regents Of The University Of California Methods of treating egfrviii expressing glioblastomas
EP3549597A1 (en) * 2018-04-06 2019-10-09 Heinrich-Heine-Universität Düsseldorf Synthetic signalling constructs and its use
CN116836297A (zh) * 2018-04-12 2023-10-03 上海赛比曼生物科技有限公司 靶向bcma的嵌合抗原受体及其制法和应用
JP7444790B2 (ja) * 2018-05-16 2024-03-06 ヤンセン バイオテツク，インコーポレーテツド 癌を治療する方法及びｔ細胞リダイレクト治療薬の有効性を向上させる方法
US20210371932A1 (en) 2018-06-01 2021-12-02 Massachusetts Institute Of Technology Methods and compositions for detecting and modulating microenvironment gene signatures from the csf of metastasis patients
CN110606893B (zh) * 2018-06-15 2022-11-15 北昊干细胞与再生医学研究院有限公司 一种靶向cd19和cd20双抗原的嵌合性抗原受体t细胞***的方法
SG11202011597RA (en) * 2018-07-20 2020-12-30 Teneobio Inc Heavy chain antibodies binding to cd19
WO2020030979A2 (en) * 2018-08-10 2020-02-13 Sangamo Therapeutics France New car constructs comprising tnfr2 domains
GB201813178D0 (en) * 2018-08-13 2018-09-26 Autolus Ltd Cell
JP7289562B2 (ja) * 2018-08-24 2023-06-12 シェンチェン プレジーン バイオファルマ カンパニー リミテッド 抗ｂｃｍａ単一ドメイン抗体及びその適用
CN109134665B (zh) * 2018-08-24 2021-06-11 上海先博生物科技有限公司 一种基于单域抗体的bcma嵌合抗原受体及应用
JP2021534783A (ja) 2018-08-31 2021-12-16 ノバルティス アーゲー キメラ抗原受容体発現細胞を作製する方法
US20210171909A1 (en) 2018-08-31 2021-06-10 Novartis Ag Methods of making chimeric antigen receptor?expressing cells
EP3850013A4 (en) * 2018-09-10 2022-10-05 Nanjing Legend Biotech Co., Ltd. SINGLE DOMAIN ANTIBODIES AGAINST CLL1 AND THEIR CONSTRUCTS
CN109293781A (zh) * 2018-09-12 2019-02-01 中国人民解放军总医院 嵌合抗原受体及其基因和重组表达载体、cd19-cd20双靶向性的t细胞及其应用
CN109081870B (zh) * 2018-09-21 2021-12-03 成都阿帕克生物科技有限公司 一种抗人促绒毛膜***β亚单位的纳米抗体及核酸分子和应用
CN109265550B (zh) * 2018-09-25 2020-09-15 华东师范大学 Bcma抗体、嵌合抗原受体和药物
MX2021003554A (es) 2018-09-25 2021-05-27 Harpoon Therapeutics Inc Proteinas de union a dll3 y metodos de uso.
JP2022501067A (ja) * 2018-09-26 2022-01-06 上海恒潤達生生物科技有限公司Hrain Biotechnology Co., Ltd. Ｂｃｍａ及びｃｄ１９を標的とするキメラ抗原受容体、並びにその使用
US20210382068A1 (en) 2018-10-02 2021-12-09 Dana-Farber Cancer Institute, Inc. Hla single allele lines
CN109503716B (zh) * 2018-10-08 2021-04-27 浙江生研生物科技有限公司 一种双特异性嵌合抗原受体分子及其在肿瘤治疗上的应用
US20210380679A1 (en) * 2018-10-11 2021-12-09 Inhibrx, Inc. Dll3 single domain antibodies and therapeutic compositions thereof
WO2020081730A2 (en) 2018-10-16 2020-04-23 Massachusetts Institute Of Technology Methods and compositions for modulating microenvironment
MX2021004732A (es) * 2018-10-26 2021-06-04 Teneobio Inc Anticuerpos de cadena pesada que se unen a cd38.
WO2020092455A2 (en) 2018-10-29 2020-05-07 The Broad Institute, Inc. Car t cell transcriptional atlas
WO2020092854A2 (en) 2018-11-01 2020-05-07 Juno Therapeutics, Inc. Chimeric antigen receptors specific for g protein-coupled receptor class c group 5 member d (gprc5d)
CN109504660B (zh) * 2018-11-02 2021-08-06 温州启星生物技术有限公司 一种***car-t细胞及其构建方法和应用
CA3117978A1 (en) 2018-11-08 2020-05-14 Juno Therapeutics, Inc. Methods and combinations for treatment and t cell modulation
CN109468283A (zh) * 2018-11-30 2019-03-15 北京美康基免生物科技有限公司 一种基于cd19和bcma的双重嵌合抗原受体基因修饰的免疫细胞及其应用
CN110951689A (zh) * 2018-11-30 2020-04-03 北京美康基免生物科技有限公司 一种基于cd19和cd30的双重嵌合抗原受体基因修饰的免疫细胞及其应用
CA3177829A1 (en) * 2018-12-12 2020-06-18 Kite Pharma, Inc. Chimeric antigen and t cell receptors and methods of use
US20220062394A1 (en) 2018-12-17 2022-03-03 The Broad Institute, Inc. Methods for identifying neoantigens
CN109485732B (zh) * 2018-12-20 2021-09-24 四川大学华西医院 基因工程修饰的双靶点嵌合抗原受体及其用途
CN109651511B (zh) * 2018-12-26 2020-06-09 广州百暨基因科技有限公司 一种靶向bcma的嵌合抗原受体及其应用
CN109652379B (zh) * 2018-12-29 2022-08-16 博生吉医药科技(苏州)有限公司 Cd7嵌合抗原受体修饰的nk-92mi细胞及其应用
CN109485734B (zh) * 2018-12-30 2020-05-12 广州百暨基因科技有限公司 一种靶向bcma和cd19的双特异性嵌合抗原受体及其应用
US11739156B2 (en) 2019-01-06 2023-08-29 The Broad Institute, Inc. Massachusetts Institute of Technology Methods and compositions for overcoming immunosuppression
EP3908613A4 (en) * 2019-01-07 2022-10-19 Celluris Participações Ltda. TANDEM BISPECIFIC CAR RECEPTOR AND METHOD FOR MODULATING A TUMOR MICROENVIRONMENT
CN109678961A (zh) * 2019-01-15 2019-04-26 深圳市南科生物工程有限公司 一种基于bmca纳米抗体序列的嵌合抗原受体的构建方法及其应用
CN113330038A (zh) * 2019-01-22 2021-08-31 亘喜生物科技（上海）有限公司 Cd20组合靶向的工程化免疫细胞
AU2020212534A1 (en) 2019-01-22 2021-07-22 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services High affinity monoclonal antibodies targeting glypican-1 and methods of use
JP2022519120A (ja) * 2019-02-04 2022-03-18 ミネルヴァ バイオテクノロジーズ コーポレーション 抗ｎｍｅ抗体および癌または癌転移の治療方法
CN109734814A (zh) * 2019-02-12 2019-05-10 南京卡提医学科技有限公司 具有免疫受体的工程化t细胞治疗癌症的用途
SG11202107825WA (en) 2019-02-25 2021-09-29 Novartis Ag Mesoporous silica particles compositions for viral delivery
WO2020186101A1 (en) 2019-03-12 2020-09-17 The Broad Institute, Inc. Detection means, compositions and methods for modulating synovial sarcoma cells
WO2020191079A1 (en) 2019-03-18 2020-09-24 The Broad Institute, Inc. Compositions and methods for modulating metabolic regulators of t cell pathogenicity
US20230074800A1 (en) 2019-03-21 2023-03-09 Novartis Ag Car-t cell therapies with enhanced efficacy
JP2022526738A (ja) 2019-03-21 2022-05-26 リジェネロン・ファーマシューティカルズ・インコーポレイテッド アレルギーを治療するためのｉｌ－４／ｉｌ－１３経路阻害剤と形質細胞除去の組み合わせ
EP3953455A1 (en) 2019-04-12 2022-02-16 Novartis AG Methods of making chimeric antigen receptor-expressing cells
CN109942709B (zh) * 2019-04-22 2019-12-27 广州百暨基因科技有限公司 一种抗bcma的单域抗体及其应用
EP3959320A1 (en) 2019-04-24 2022-03-02 Novartis AG Compositions and methods for selective protein degradation
EP3733707A1 (en) 2019-04-30 2020-11-04 Celyad S.A. Car t-cells targeting bcma and uses thereof
MX2021013416A (es) * 2019-05-04 2021-12-10 Inhibrx Inc Polipeptidos de union al antigeno cd33 y sus usos.
WO2020236967A1 (en) 2019-05-20 2020-11-26 The Broad Institute, Inc. Random crispr-cas deletion mutant
CN114206919A (zh) * 2019-06-04 2022-03-18 综合医院公司 靶向taci的抗体和嵌合抗原受体
JOP20210323A1 (ar) 2019-06-14 2023-01-30 Teneobio Inc ارتباط أجسام مضادة ثقيلة السلسلة ومتعددة النوعية بـ cd22 وcd3
WO2020261219A1 (en) * 2019-06-27 2020-12-30 Crispr Therapeutics Ag Use of chimeric antigen receptor t cells and nk cell inhibitors for treating cancer
US20220282333A1 (en) 2019-08-13 2022-09-08 The General Hospital Corporation Methods for predicting outcomes of checkpoint inhibition and treatment thereof
CN110540997B (zh) * 2019-08-29 2024-02-13 浙江煦顼技术有限公司 靶向bcma嵌合抗原受体、核酸序列、载体及应用
US20220298501A1 (en) 2019-08-30 2022-09-22 The Broad Institute, Inc. Crispr-associated mu transposase systems
US20210164045A1 (en) * 2019-08-30 2021-06-03 Janssen Biotech, Inc. B-cell maturation complex car t construct and primers
WO2021043169A1 (zh) * 2019-09-02 2021-03-11 成都盛世君联生物技术有限公司 特异性结合b细胞成熟抗原的抗体及其用途
US20220333079A1 (en) * 2019-09-18 2022-10-20 Slbigen Inc. Genetically modified nk cell line transduced with gene encoding novel chimeric antigen receptor and use thereof
CN112739721B (zh) * 2019-09-26 2023-01-31 苏州克睿基因生物科技有限公司 一种单域抗体及包含抗体结构的嵌合抗原受体
US11793787B2 (en) 2019-10-07 2023-10-24 The Broad Institute, Inc. Methods and compositions for enhancing anti-tumor immunity by targeting steroidogenesis
WO2021081133A1 (en) * 2019-10-21 2021-04-29 Purdue Research Foundation Engineered natural killer cells and methods for using the same in immunotherapy and autophagy inhibition techniques
CA3156761A1 (en) 2019-10-22 2021-04-29 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services High affinity nanobodies targeting b7h3 (cd276) for treating multiple solid tumors
US11844800B2 (en) 2019-10-30 2023-12-19 Massachusetts Institute Of Technology Methods and compositions for predicting and preventing relapse of acute lymphoblastic leukemia
BR112022008633A2 (pt) 2019-11-05 2022-07-19 Janssen Biotech Inc Terapia de células car-t direcionadas a bcma de mieloma múltiplo
EP4065606A4 (en) * 2019-11-26 2023-08-02 Ramot at Tel-Aviv University Ltd. CHIMERIC ANTIGEN RECEPTOR FOR CARBOHYDRATES
MX2022006391A (es) 2019-11-26 2022-06-24 Novartis Ag Receptores de antigeno quimerico que se unen a bcma y cd19 y usos de los mismos.
US20230058669A1 (en) * 2019-12-16 2023-02-23 Nanjing Legend Biotech Co., Ltd. Single domain antibodies and chimeric antigen receptors targeting bcma and methods of use thereof
CN111171158B (zh) * 2020-01-17 2020-10-30 南京蓝盾生物科技有限公司 同时靶向bcma和cd38的嵌合抗原受体及其应用
CN111235113A (zh) * 2020-01-21 2020-06-05 南京北恒生物科技有限公司 包含嵌合抗原受体的免疫细胞及其用途
EP4097220A4 (en) * 2020-01-30 2024-03-20 Immunitybio Inc ELIMINATION OF BCMA-POSITIVE MALIGNANCIES BY CAR-EXPRESSING NK CELLS
CN111196858B (zh) * 2020-02-05 2021-02-09 武汉科技大学 一种治疗血液肿瘤合并hiv感染的双特异性嵌合抗原受体、基因、构建方法及其应用
CA3167572A1 (en) * 2020-02-14 2021-08-19 Robbie G. MAJZNER Chimeric antigen receptors with cd2 activation
CA3173737A1 (en) 2020-02-27 2021-09-02 Novartis Ag Methods of making chimeric antigen receptor-expressing cells
IL295604A (en) 2020-02-27 2022-10-01 Novartis Ag Methods for producing cells expressing a chimeric antigen receptor
CN113402612A (zh) * 2020-03-17 2021-09-17 西比曼生物科技（香港）有限公司 靶向cd19和cd20的联合嵌合抗原受体及其应用
CA3179800A1 (en) 2020-04-10 2021-10-14 Juno Therapeutics, Inc. Methods and uses related to cell therapy engineered with a chimeric antigen receptor targeting b-cell maturation antigen
WO2021222330A2 (en) 2020-04-28 2021-11-04 Juno Therapeutics, Inc. Combination of bcma-directed t cell therapy and an immunomodulatory compound
MX2022013453A (es) 2020-04-29 2022-11-16 Teneobio Inc Anticuerpos de cadena pesada multiespecificos con regiones constantes de cadena pesada modificadas.
WO2021223705A1 (en) * 2020-05-06 2021-11-11 Gracell Biotechnologies (Shanghai) Co., Ltd. Compositions and methods for t cell engineering
CN111574629B (zh) * 2020-06-01 2021-07-20 宁夏医科大学 一种抗cd20的纳米抗体、编码基因、重组纳米抗体、重组载体、重组菌株和应用
CN111607565A (zh) * 2020-06-04 2020-09-01 河南大学 一种北平顶猴t细胞的体外扩增方法
AU2021288224A1 (en) 2020-06-11 2023-01-05 Novartis Ag ZBTB32 inhibitors and uses thereof
US11497770B2 (en) 2020-06-22 2022-11-15 Lentigen Technology, Inc. Compositions and methods for treating cancer with TSLPR-CD19 or TSLPR-CD22 immunotherapy
EP4172215A2 (en) * 2020-06-26 2023-05-03 Minerva Biotechnologies Corporation Anti-nme antibody and method of treating cancer or cancer metastasis
CN114222761B (zh) * 2020-07-14 2024-02-20 浙江道尔生物科技有限公司 一种抗cld18a2的单域抗体
AU2021308745A1 (en) * 2020-07-16 2023-02-16 Legend Biotech Ireland Limited Multispecific chimeric antigen receptors and uses thereof
CN111848798B (zh) * 2020-07-27 2022-05-13 源道隆（苏州）医学科技有限公司 可结合bcma的纳米抗体及其应用
CN111909271B (zh) * 2020-08-12 2021-03-23 深圳市茵冠生物科技有限公司 一种基于单域抗体的bcma嵌合抗原受体及其应用
CN116390946A (zh) 2020-08-13 2023-07-04 美国政府(由卫生和人类服务部的部长所代表) 用于治疗实体瘤的靶向磷脂酰肌醇蛋白聚糖-1（gpc1）的含igg4铰链的嵌合抗原受体
US20230193292A1 (en) 2020-08-20 2023-06-22 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Bcma-binding single variable structural domain and antigen-binding molecule
EP4201960A1 (en) 2020-08-20 2023-06-28 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Single variable domain and antigen binding molecule binding bcma
EP4199960A2 (en) 2020-08-21 2023-06-28 Novartis AG Compositions and methods for in vivo generation of car expressing cells
CN112062864A (zh) * 2020-09-18 2020-12-11 樊克兴 靶向bcma肿瘤抗原受体修饰t细胞的制备方法和应用
CN111925451B (zh) * 2020-10-12 2021-01-29 佑仁细胞工程(浙江)有限公司 一种靶向bcma的嵌合抗原受体(car)及其应用
CN112251412B (zh) * 2020-10-12 2023-03-28 汤朝阳 一种靶向bcma的嵌合抗原受体t细胞及其应用
WO2022093745A1 (en) 2020-10-26 2022-05-05 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Single domain antibodies targeting sars coronavirus spike protein and uses thereof
CN112028996B (zh) * 2020-10-30 2021-01-22 南京北恒生物科技有限公司 靶向bcma的单域抗体及其用途
WO2022098787A1 (en) 2020-11-04 2022-05-12 Juno Therapeutics, Inc. Cells expressing a chimeric receptor from a modified invariant cd3 immunoglobulin superfamily chain locus and related polynucleotides and methods
WO2022116086A1 (en) 2020-12-03 2022-06-09 Janssen Biotech, Inc. Bcma-targeted car-t cell therapy for multiple myeloma
WO2022120160A1 (en) 2020-12-04 2022-06-09 Celgene Corporation Uses of chimeric antigen receptor (car) t-cell therapies in combination with inhibitors of inflammation-related soluble factors
TW202237638A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 烏苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
TW202237639A (zh) 2020-12-09 2022-10-01 日商武田藥品工業股份有限公司 鳥苷酸環化酶ｃ（ｇｃｃ）抗原結合劑之組成物及其使用方法
WO2022140388A1 (en) 2020-12-21 2022-06-30 Allogene Therapeutics, Inc. Protease-activating cd45-gate car
CN116390954A (zh) * 2020-12-29 2023-07-04 宁波茂行生物医药科技有限公司 靶向bcma的单域抗体
KR20230137900A (ko) 2020-12-31 2023-10-05 사나 바이오테크놀로지, 인크. Car-t 활성을 조정하기 위한 방법 및 조성물
CN112321713B (zh) * 2020-12-31 2021-05-25 北京艺妙神州医药科技有限公司 一种抗bcma的抗体及其应用
JP2024503027A (ja) 2021-01-11 2024-01-24 サナ バイオテクノロジー，インコーポレイテッド Ｃｄ８標的ウイルスベクターの使用方法
CN114149505B (zh) * 2021-01-12 2022-11-04 北京门罗生物科技有限公司 治疗b细胞相关疾病的免疫细胞、制备方法及其应用
CN112778427B (zh) * 2021-01-29 2022-03-15 武汉思安医疗技术有限公司 双特异性cs1-bcma car-t细胞及其应用
CA3204417A1 (en) 2021-01-29 2022-08-04 Allogene Therapeutics, Inc. Knockdown or knockout of one or more of tap2, nlrc5, ?2m, trac, rfx5, rfxap and rfxank to mitigate t cell recognition of allogeneic cell products
WO2022172085A2 (en) 2021-02-15 2022-08-18 Takeda Pharmaceutical Company Limited Cell therapy compositions and methods for modulating tgf-b signaling
WO2022183160A1 (en) * 2021-02-25 2022-09-01 H. Lee Moffitt Cancer Center And Research Institute Inc. Methods for treating cd83-expressing cancer
KR20230165771A (ko) 2021-03-03 2023-12-05 주노 쎄러퓨티크스 인코퍼레이티드 T 세포 요법 및 dgk 억제제의 조합
CN115109156B (zh) * 2021-03-22 2024-03-08 浙江纳米抗体技术中心有限公司 一种靶向bcma的纳米抗体及其应用
WO2022216864A1 (en) * 2021-04-06 2022-10-13 Teneobio, Inc. Anti-cd19 antibodies and car-t structures
CN117730091A (zh) * 2021-04-13 2024-03-19 悟境股份有限公司 改善的嵌合抗原受体及其用途
CA3214012A1 (en) 2021-04-15 2022-10-20 Bing Zhang Multi-specific antibody targeting bcma
EP4322959A2 (en) 2021-04-16 2024-02-21 Celgene Corporation Combination therapies with bcma-directed t cell therapy
AU2022259688A1 (en) * 2021-04-16 2023-10-05 Teneobio, Inc. Anti-cd20 antibodies and car-t structures
WO2022221737A1 (en) 2021-04-16 2022-10-20 Juno Therapeutics, Inc. T cell therapy in patients who have had prior stem cell transplant
EP4330381A1 (en) 2021-04-27 2024-03-06 Novartis AG Viral vector production system
WO2022232612A1 (en) 2021-04-29 2022-11-03 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Lassa virus-specific nanobodies and methods of their use
WO2022228579A1 (en) * 2021-04-30 2022-11-03 Nanjing Legend Biotech Co., Ltd. Chimeric antigen receptors targeting gpc3 and methods of use thereof
WO2022234009A2 (en) 2021-05-06 2022-11-10 Juno Therapeutics Gmbh Methods for stimulating and transducing t cells
TW202309522A (zh) 2021-05-11 2023-03-01 美商健生生物科技公司 用於監測復發性及／或難治性多發性骨髓瘤之治療的方法及組成物
BR112023023269A2 (pt) 2021-05-11 2024-01-30 Janssen Biotech Inc Métodos de minimização de neurotoxicidade associada à terapia com células t do receptor de antígeno quimérico (car)
WO2022246004A1 (en) * 2021-05-19 2022-11-24 Celledit Llc Bi-specific chimeric antigen receptors and genetically engineered immune cells expressing such
EP4340851A1 (en) 2021-05-19 2024-03-27 Sana Biotechnology, Inc. Hypoimmunogenic rhd negative primary t cells
KR20240013135A (ko) 2021-05-27 2024-01-30 사나 바이오테크놀로지, 인크. 조작된 hla-e 또는 hla-g를 포함하는 저면역원성 세포
EP4352099A1 (en) 2021-06-09 2024-04-17 The United States of America, as represented by The Secretary, Department of Health and Human Services Cross species single domain antibodies targeting pd-l1 for treating solid tumors
CA3225985A1 (en) 2021-07-01 2023-01-05 Indapta Therapeutics, Inc. Engineered natural killer (nk) cells and related methods
KR20240034234A (ko) 2021-07-14 2024-03-13 2세븐티 바이오, 인코포레이티드 항체로부터의 결합 도메인에 융합된 조작된 t 세포 수용체
AU2022309875A1 (en) 2021-07-14 2024-01-25 Sana Biotechnology, Inc. Altered expression of y chromosome-linked antigens in hypoimmunogenic cells
WO2023015217A1 (en) 2021-08-04 2023-02-09 Sana Biotechnology, Inc. Use of cd4-targeted viral vectors
WO2023019203A1 (en) 2021-08-11 2023-02-16 Sana Biotechnology, Inc. Inducible systems for altering gene expression in hypoimmunogenic cells
CA3228773A1 (en) * 2021-08-12 2023-02-16 Gaurav KHARYA Chimeric antigen receptors (car) for b cell malignancies
CN113651893B (zh) * 2021-08-12 2023-08-01 上海生物制品研究所有限责任公司 联合her2和meso双靶点car-t载体及其构建方法和在癌症中的应用
AU2022330406A1 (en) 2021-08-20 2024-03-07 Novartis Ag Methods of making chimeric antigen receptor–expressing cells
US11359012B1 (en) 2021-08-27 2022-06-14 Nanjing Kaedi Biotherapeutics Ltd. Specific chimeric antigen receptor cells targeting human CLDN18A2, preparation method and application thereof
CN117586404A (zh) * 2021-09-24 2024-02-23 四川大学 可特异性靶向人EpCAM抗原的纳米抗体及应用
US20230227553A1 (en) * 2021-09-29 2023-07-20 Modex Therapeutics Antigen binding polypeptides, antigen binding polypeptide complexes and methods of use thereof
WO2023056555A1 (en) * 2021-10-07 2023-04-13 National Research Council Of Canada Anti-bcma single domain antibodies and therapeutic constructs
WO2023069790A1 (en) 2021-10-22 2023-04-27 Sana Biotechnology, Inc. Methods of engineering allogeneic t cells with a transgene in a tcr locus and associated compositions and methods
WO2023076881A1 (en) 2021-10-26 2023-05-04 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Single domain antibodies targeting the s2 subunit of sars-cov-2 spike protein
CN114015674A (zh) 2021-11-02 2022-02-08 辉二(上海)生物科技有限公司 新型CRISPR-Cas12i***
US20230136301A1 (en) 2021-11-03 2023-05-04 Janssen Biotech, Inc. Corticosteriod Reduction in Treatment with Anti-CD38 Antibody
WO2023081735A1 (en) 2021-11-03 2023-05-11 Celgene Corporation Chimeric antigen receptors specific for b-cell maturation antigen for use in treating myeloma
WO2023077343A1 (en) 2021-11-04 2023-05-11 Janssen Biotech, Inc. Bcma-targeted car-t cell therapy for multiple myeloma
US20230277589A1 (en) 2021-11-04 2023-09-07 Janssen Biotech, Inc. Bcma-targeted car-t cell therapy for multiple myeloma
WO2023086829A1 (en) 2021-11-09 2023-05-19 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Igg4 hinge-containing chimeric antigen receptors targeting glypican-3 (gpc3) and use thereof
CN115466331B (zh) * 2021-11-18 2023-05-30 合源生物科技(天津)有限公司 靶向bcma的嵌合抗原受体及其应用
CN116284385A (zh) * 2021-12-07 2023-06-23 信达细胞制药(苏州)有限公司 靶向bcma的p329g抗体及其与嵌合抗原受体细胞的组合和应用
CN114195898B (zh) * 2021-12-13 2022-10-28 南京凯地医疗技术有限公司 人源化抗cd33的单域抗体及其构建体制备方法和应用
WO2023109257A1 (zh) * 2021-12-16 2023-06-22 浙江瑞加美生物科技有限公司 人源化的bcma抗体和bcma-car-t/bcma-car-dnt细胞
WO2023115041A1 (en) 2021-12-17 2023-06-22 Sana Biotechnology, Inc. Modified paramyxoviridae attachment glycoproteins
TW202342498A (zh) 2021-12-17 2023-11-01 美商薩那生物科技公司 經修飾副黏液病毒科融合醣蛋白
WO2023122337A1 (en) 2021-12-23 2023-06-29 Sana Biotechnology, Inc. Chimeric antigen receptor (car) t cells for treating autoimmune disease and associated methods
WO2023129819A2 (en) * 2021-12-29 2023-07-06 Rutgers, The State University Of New Jersey Single-domain high affinity antibodies and methods of use thereof
WO2023133595A2 (en) 2022-01-10 2023-07-13 Sana Biotechnology, Inc. Methods of ex vivo dosing and administration of lipid particles or viral vectors and related systems and uses
WO2023147515A1 (en) 2022-01-28 2023-08-03 Juno Therapeutics, Inc. Methods of manufacturing cellular compositions
WO2023150518A1 (en) 2022-02-01 2023-08-10 Sana Biotechnology, Inc. Cd3-targeted lentiviral vectors and uses thereof
WO2023150647A1 (en) 2022-02-02 2023-08-10 Sana Biotechnology, Inc. Methods of repeat dosing and administration of lipid particles or viral vectors and related systems and uses
WO2023158986A1 (en) 2022-02-15 2023-08-24 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Cd28 hinge and transmembrane containing chimeric antigen receptors targeting gpc2 and use thereof
WO2023158836A1 (en) 2022-02-17 2023-08-24 Sana Biotechnology, Inc. Engineered cd47 proteins and uses thereof
WO2023164695A2 (en) 2022-02-28 2023-08-31 Janssen Biotech, Inc. Bcma-targeted car-t cell therapy for multiple myeloma
WO2023193015A1 (en) 2022-04-01 2023-10-05 Sana Biotechnology, Inc. Cytokine receptor agonist and viral vector combination therapies
WO2023196997A2 (en) 2022-04-08 2023-10-12 2Seventy Bio, Inc. Multipartite receptor and signaling complexes
CN114685664B (zh) * 2022-04-12 2023-10-20 内蒙古农业大学 抗人b淋巴细胞表面抗原cd20的单域抗体及其应用
WO2023213969A1 (en) 2022-05-05 2023-11-09 Juno Therapeutics Gmbh Viral-binding protein and related reagents, articles, and methods of use
WO2023217067A1 (zh) * 2022-05-09 2023-11-16 上海先博生物科技有限公司 工程化免疫效应细胞及其与CBL-b抑制剂联用的应用
WO2023220641A2 (en) 2022-05-11 2023-11-16 Juno Therapeutics, Inc. Methods and uses related to t cell therapy and production of same
WO2023220655A1 (en) 2022-05-11 2023-11-16 Celgene Corporation Methods to overcome drug resistance by re-sensitizing cancer cells to treatment with a prior therapy via treatment with a t cell therapy
WO2023230581A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Methods of manufacturing t cell therapies
WO2023230548A1 (en) 2022-05-25 2023-11-30 Celgene Corporation Method for predicting response to a t cell therapy
CN117279949A (zh) * 2022-05-27 2023-12-22 苏州易慕峰生物科技有限公司 包含cldn18.2单域抗体的嵌合抗原受体及其应用
WO2023244547A1 (en) * 2022-06-13 2023-12-21 The Regents Of The University Of California Humanized antibodies to human integrin avb8
US20240052049A1 (en) * 2022-06-24 2024-02-15 Orna Therapeutics, Inc. Circular rna encoding chimeric antigen receptors targeting bcma
CN114805582B (zh) * 2022-06-29 2022-10-04 上海恒润达生生物科技股份有限公司 抗Trop2纳米抗体及其用途
WO2024007020A1 (en) 2022-06-30 2024-01-04 Indapta Therapeutics, Inc. Combination of engineered natural killer (nk) cells and antibody therapy and related methods
WO2024026377A1 (en) 2022-07-27 2024-02-01 Sana Biotechnology, Inc. Methods of transduction using a viral vector and inhibitors of antiviral restriction factors
US20240042030A1 (en) 2022-07-29 2024-02-08 Allogene Therapeutics, Inc. Engineered cells with reduced gene expression to mitigate immune cell recognition
US20240041929A1 (en) 2022-08-05 2024-02-08 Juno Therapeutics, Inc. Chimeric antigen receptors specific for gprc5d and bcma
WO2024041650A1 (en) * 2022-08-25 2024-02-29 Nanjing Legend Biotech Co., Ltd. Chimeric antigen receptors targeting interleukin 13 receptor subunit alpha 2 and methods of use thereof
WO2024050399A1 (en) 2022-09-01 2024-03-07 The United States Of America, As Represented By The Secretary, Department Of Health And Human Services Single domain antibodies targeting hpv e6/e7 oncogenic peptide/mhc complexes
CN116023495B (zh) * 2022-09-05 2023-10-03 上海百英生物科技股份有限公司 一种抗cd40纳米抗体及其制备方法与应用
WO2024054944A1 (en) 2022-09-08 2024-03-14 Juno Therapeutics, Inc. Combination of a t cell therapy and continuous or intermittent dgk inhibitor dosing
WO2024064838A1 (en) 2022-09-21 2024-03-28 Sana Biotechnology, Inc. Lipid particles comprising variant paramyxovirus attachment glycoproteins and uses thereof
CN115925947B (zh) * 2022-09-27 2023-08-22 上海百英生物科技股份有限公司 一种亲和力成熟方法及抗人pd-l1单域抗体的亲和力成熟
CN116120465B (zh) * 2022-11-01 2023-10-13 邦恩泰(山东)生物医药科技集团股份有限公司 一种靶向bcma和/或fcrh5的嵌合抗原受体及其应用
CN117069844B (zh) * 2022-12-06 2024-02-09 成都赛恩吉诺生物科技有限公司 包含特定等电点的抗人bcma纳米抗体的双特异性抗体及应用
CN116199781A (zh) * 2023-02-22 2023-06-02 成都优赛诺生物科技有限公司 一种靶向cd22的单域抗体、嵌合抗原受体及其应用
CN116640229B (zh) * 2023-04-10 2024-01-30 中国人民解放军总医院第五医学中心 一种低pH靶向性CAR-T细胞的构建及应用
CN116655805B (zh) * 2023-05-31 2024-03-08 四川大学华西医院 一种靶向her2阳性肿瘤的新型car-t细胞及制备方法和应用
CN116789859B (zh) * 2023-06-29 2024-02-23 徐州医科大学 一种用于评价bcma靶向car-t细胞药效的靶细胞及其应用
CN116949099B (zh) * 2023-07-12 2024-04-02 山东大学第二医院 一种靶向cd38和cs1抗原的并联嵌合抗原受体t细胞及其制备方法和应用
CN117024594A (zh) * 2023-09-21 2023-11-10 武汉波睿达生物科技有限公司 一种抗cd20的纳米抗体及其应用

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104583230A (zh) * 2012-07-13 2015-04-29 宾夕法尼亚大学董事会 通过共同引入双特异性抗体增强car t细胞的活性

Family Cites Families (187)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US30985A (en) 1860-12-18 Thomas l
FR901228A (fr) 1943-01-16 1945-07-20 Deutsche Edelstahlwerke Ag Système d'aimant à entrefer annulaire
US3773919A (en) 1969-10-23 1973-11-20 Du Pont Polylactide-drug mixtures
USRE30985E (en) 1978-01-01 1982-06-29 Serum-free cell culture media
US4657760A (en) 1979-03-20 1987-04-14 Ortho Pharmaceutical Corporation Methods and compositions using monoclonal antibody to human T cells
US4419446A (en) 1980-12-31 1983-12-06 The United States Of America As Represented By The Department Of Health And Human Services Recombinant DNA process utilizing a papilloma virus DNA as a vector
US4601978A (en) 1982-11-24 1986-07-22 The Regents Of The University Of California Mammalian metallothionein promoter system
US4560655A (en) 1982-12-16 1985-12-24 Immunex Corporation Serum-free cell culture medium and process for making same
US4657866A (en) 1982-12-21 1987-04-14 Sudhir Kumar Serum-free, synthetic, completely chemically defined tissue culture media
US4816567A (en) 1983-04-08 1989-03-28 Genentech, Inc. Recombinant immunoglobin preparations
US4767704A (en) 1983-10-07 1988-08-30 Columbia University In The City Of New York Protein-free culture medium
US4965199A (en) 1984-04-20 1990-10-23 Genentech, Inc. Preparation of functional human factor VIII in mammalian cells using methotrexate based selection
US4737456A (en) 1985-05-09 1988-04-12 Syntex (U.S.A.) Inc. Reducing interference in ligand-receptor binding assays
US5206344A (en) 1985-06-26 1993-04-27 Cetus Oncology Corporation Interleukin-2 muteins and polymer conjugation thereof
GB8516415D0 (en) 1985-06-28 1985-07-31 Celltech Ltd Culture of animal cells
US4676980A (en) 1985-09-23 1987-06-30 The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Target specific cross-linked heteroantibodies
US6548640B1 (en) 1986-03-27 2003-04-15 Btg International Limited Altered antibodies
US4927762A (en) 1986-04-01 1990-05-22 Cell Enterprises, Inc. Cell culture medium with antioxidant
IL85035A0 (en) 1987-01-08 1988-06-30 Int Genetic Eng Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same
DE3883899T3 (de) 1987-03-18 1999-04-22 Sb2 Inc Geänderte antikörper.
US5770701A (en) 1987-10-30 1998-06-23 American Cyanamid Company Process for preparing targeted forms of methyltrithio antitumor agents
US5606040A (en) 1987-10-30 1997-02-25 American Cyanamid Company Antitumor and antibacterial substituted disulfide derivatives prepared from compounds possessing a methyl-trithio group
ATE135397T1 (de) 1988-09-23 1996-03-15 Cetus Oncology Corp Zellenzuchtmedium für erhöhtes zellenwachstum, zur erhöhung der langlebigkeit und expression der produkte
GB8823869D0 (en) 1988-10-12 1988-11-16 Medical Res Council Production of antibodies
JP2919890B2 (ja) 1988-11-11 1999-07-19 メディカル リサーチ カウンスル 単一ドメインリガンド、そのリガンドからなる受容体、その製造方法、ならびにそのリガンドおよび受容体の使用
US6905680B2 (en) 1988-11-23 2005-06-14 Genetics Institute, Inc. Methods of treating HIV infected subjects
US6352694B1 (en) 1994-06-03 2002-03-05 Genetics Institute, Inc. Methods for inducing a population of T cells to proliferate using agents which recognize TCR/CD3 and ligands which stimulate an accessory molecule on the surface of the T cells
US6534055B1 (en) 1988-11-23 2003-03-18 Genetics Institute, Inc. Methods for selectively stimulating proliferation of T cells
US5858358A (en) 1992-04-07 1999-01-12 The United States Of America As Represented By The Secretary Of The Navy Methods for selectively stimulating proliferation of T cells
DE3920358A1 (de) 1989-06-22 1991-01-17 Behringwerke Ag Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung
US5225212A (en) 1989-10-20 1993-07-06 Liposome Technology, Inc. Microreservoir liposome composition and method
US5208020A (en) 1989-10-25 1993-05-04 Immunogen Inc. Cytotoxic agents comprising maytansinoids and their therapeutic use
CA2026147C (en) 1989-10-25 2006-02-07 Ravi J. Chari Cytotoxic agents comprising maytansinoids and their therapeutic use
US6150584A (en) 1990-01-12 2000-11-21 Abgenix, Inc. Human antibodies derived from immunized xenomice
US6075181A (en) 1990-01-12 2000-06-13 Abgenix, Inc. Human antibodies derived from immunized xenomice
EP1690935A3 (en) 1990-01-12 2008-07-30 Abgenix, Inc. Generation of xenogeneic antibodies
US5633425A (en) 1990-08-29 1997-05-27 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
KR100272077B1 (ko) 1990-08-29 2000-11-15 젠팜인터내셔날,인코포레이티드 이종 항체를 생산할 수 있는 전이유전자를 가진 인간이외의 동물
US5545806A (en) 1990-08-29 1996-08-13 Genpharm International, Inc. Ransgenic non-human animals for producing heterologous antibodies
US5625126A (en) 1990-08-29 1997-04-29 Genpharm International, Inc. Transgenic non-human animals for producing heterologous antibodies
US5770429A (en) 1990-08-29 1998-06-23 Genpharm International, Inc. Transgenic non-human animals capable of producing heterologous antibodies
US5661016A (en) 1990-08-29 1997-08-26 Genpharm International Inc. Transgenic non-human animals capable of producing heterologous antibodies of various isotypes
US5122469A (en) 1990-10-03 1992-06-16 Genentech, Inc. Method for culturing Chinese hamster ovary cells to improve production of recombinant proteins
US5508192A (en) 1990-11-09 1996-04-16 Board Of Regents, The University Of Texas System Bacterial host strains for producing proteolytically sensitive polypeptides
US5264365A (en) 1990-11-09 1993-11-23 Board Of Regents, The University Of Texas System Protease-deficient bacterial strains for production of proteolytically sensitive polypeptides
ATE164395T1 (de) 1990-12-03 1998-04-15 Genentech Inc Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften
US5571894A (en) 1991-02-05 1996-11-05 Ciba-Geigy Corporation Recombinant antibodies specific for a growth factor receptor
DK0590058T3 (da) 1991-06-14 2004-03-29 Genentech Inc Humaniseret heregulin-antistof
GB9114948D0 (en) 1991-07-11 1991-08-28 Pfizer Ltd Process for preparing sertraline intermediates
WO1993006217A1 (en) 1991-09-19 1993-04-01 Genentech, Inc. EXPRESSION IN E. COLI OF ANTIBODY FRAGMENTS HAVING AT LEAST A CYSTEINE PRESENT AS A FREE THIOL, USE FOR THE PRODUCTION OF BIFUNCTIONAL F(ab')2 ANTIBODIES
US5587458A (en) 1991-10-07 1996-12-24 Aronex Pharmaceuticals, Inc. Anti-erbB-2 antibodies, combinations thereof, and therapeutic and diagnostic uses thereof
WO1993008829A1 (en) 1991-11-04 1993-05-13 The Regents Of The University Of California Compositions that mediate killing of hiv-infected cells
JPH07501451A (ja) 1991-11-25 1995-02-16 エンゾン・インコーポレイテッド 多価抗原結合タンパク質
EP1997894B1 (en) 1992-02-06 2011-03-30 Novartis Vaccines and Diagnostics, Inc. Biosynthetic binding protein for cancer marker
DE69330523D1 (de) 1992-08-21 2001-09-06 Vrije Universiteit Brussel Bru Immunoglobuline ohne leichte ketten
WO1994011026A2 (en) 1992-11-13 1994-05-26 Idec Pharmaceuticals Corporation Therapeutic application of chimeric and radiolabeled antibodies to human b lymphocyte restricted differentiation antigen for treatment of b cell lymphoma
US5635483A (en) 1992-12-03 1997-06-03 Arizona Board Of Regents Acting On Behalf Of Arizona State University Tumor inhibiting tetrapeptide bearing modified phenethyl amides
US5780588A (en) 1993-01-26 1998-07-14 Arizona Board Of Regents Elucidation and synthesis of selected pentapeptides
CA2163345A1 (en) 1993-06-16 1994-12-22 Susan Adrienne Morgan Antibodies
US7175843B2 (en) 1994-06-03 2007-02-13 Genetics Institute, Llc Methods for selectively stimulating proliferation of T cells
US5773001A (en) 1994-06-03 1998-06-30 American Cyanamid Company Conjugates of methyltrithio antitumor agents and intermediates for their synthesis
US5639635A (en) 1994-11-03 1997-06-17 Genentech, Inc. Process for bacterial production of polypeptides
US5731168A (en) 1995-03-01 1998-03-24 Genentech, Inc. Method for making heteromultimeric polypeptides
US5840523A (en) 1995-03-01 1998-11-24 Genetech, Inc. Methods and compositions for secretion of heterologous polypeptides
US5641870A (en) 1995-04-20 1997-06-24 Genentech, Inc. Low pH hydrophobic interaction chromatography for antibody purification
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
EP0739981A1 (en) 1995-04-25 1996-10-30 Vrije Universiteit Brussel Variable fragments of immunoglobulins - use for therapeutic or veterinary purposes
DE69637481T2 (de) 1995-04-27 2009-04-09 Amgen Fremont Inc. Aus immunisierten Xenomäusen stammende menschliche Antikörper gegen IL-8
EP0823941A4 (en) 1995-04-28 2001-09-19 Abgenix Inc HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES
US7067318B2 (en) 1995-06-07 2006-06-27 The Regents Of The University Of Michigan Methods for transfecting T cells
US6692964B1 (en) 1995-05-04 2004-02-17 The United States Of America As Represented By The Secretary Of The Navy Methods for transfecting T cells
US5714586A (en) 1995-06-07 1998-02-03 American Cyanamid Company Methods for the preparation of monomeric calicheamicin derivative/carrier conjugates
US5712374A (en) 1995-06-07 1998-01-27 American Cyanamid Company Method for the preparation of substantiallly monomeric calicheamicin derivative/carrier conjugates
GB9603256D0 (en) 1996-02-16 1996-04-17 Wellcome Found Antibodies
WO1997038123A1 (en) 1996-04-05 1997-10-16 Board Of Regents, The University Of Texas System Methods for producing soluble, biologically-active disulfide bond-containing eukaryotic proteins in bacterial cells
ATE374248T1 (de) 1996-06-27 2007-10-15 Vlaams Interuniv Inst Biotech Antikörpermoleküle, die spezifisch mit dem aktiven zentrum oder dem aktiven spalt eines zielmoleküls interagieren
EP2305027B1 (en) 1996-12-03 2014-07-02 Amgen Fremont Inc. Transgenic mammals having human Ig loci including plural VH and Vkappa regions and antibodies produced therefrom
US6083715A (en) 1997-06-09 2000-07-04 Board Of Regents, The University Of Texas System Methods for producing heterologous disulfide bond-containing polypeptides in bacterial cells
WO1998058964A1 (en) 1997-06-24 1998-12-30 Genentech, Inc. Methods and compositions for galactosylated glycoproteins
WO1999022764A1 (en) 1997-10-31 1999-05-14 Genentech, Inc. Methods and compositions comprising glycoprotein glycoforms
US6610833B1 (en) 1997-11-24 2003-08-26 The Institute For Human Genetics And Biochemistry Monoclonal human natural antibodies
ES2375931T3 (es) 1997-12-05 2012-03-07 The Scripps Research Institute Humanización de anticuerpo murino.
AU3596599A (en) 1998-01-26 1999-08-09 Unilever Plc Method for producing antibody fragments
JP2002510481A (ja) 1998-04-02 2002-04-09 ジェネンテック・インコーポレーテッド 抗体変異体及びその断片
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
EP2261229A3 (en) 1998-04-20 2011-03-23 GlycArt Biotechnology AG Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity
MXPA01005425A (es) 1998-12-01 2002-04-24 Genentech Inc Polipeptidos de transmembrana y secretados y acidos nucleicos que codifican los mismos.
JP2003512019A (ja) 1999-01-15 2003-04-02 ジェネンテック・インコーポレーテッド 変化したエフェクター機能を有するポリペプチド変異体
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
ATE276359T1 (de) 1999-01-19 2004-10-15 Unilever Nv Verfahren zur herstellung von antikörperfragmenten
ES2420835T3 (es) 1999-04-09 2013-08-27 Kyowa Hakko Kirin Co., Ltd. Procedimiento para controlar la actividad de las moléculas inmunofuncionales
AU4418900A (en) 1999-04-16 2000-11-02 Celltech Therapeutics Limited Synthetic transmembrane components
JP4668498B2 (ja) 1999-10-19 2011-04-13 協和発酵キリン株式会社 ポリペプチドの製造方法
WO2001044463A1 (en) 1999-12-15 2001-06-21 Genentech, Inc. Shotgun scanning, a combinatorial method for mapping functional protein epitopes
AU767394C (en) 1999-12-29 2005-04-21 Immunogen, Inc. Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use
US6797514B2 (en) 2000-02-24 2004-09-28 Xcyte Therapies, Inc. Simultaneous stimulation and concentration of cells
US6867041B2 (en) 2000-02-24 2005-03-15 Xcyte Therapies, Inc. Simultaneous stimulation and concentration of cells
AU4328801A (en) 2000-02-24 2001-09-03 Xcyte Therapies Inc Simultaneous stimulation and concentration of cells
US7572631B2 (en) 2000-02-24 2009-08-11 Invitrogen Corporation Activation and expansion of T cells
JP2003531588A (ja) 2000-04-11 2003-10-28 ジェネンテック・インコーポレーテッド 多価抗体とその用途
WO2001090190A2 (en) 2000-05-26 2001-11-29 National Research Council Of Canada Single-domain antigen-binding antibody fragments derived from llama antibodies
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
CA2953239A1 (en) 2000-10-06 2002-04-18 Kyowa Hakko Kirin Co., Ltd. Antibody composition-producing cell
US7064191B2 (en) 2000-10-06 2006-06-20 Kyowa Hakko Kogyo Co., Ltd. Process for purifying antibody
US6596541B2 (en) 2000-10-31 2003-07-22 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
CN101940189A (zh) 2000-11-30 2011-01-12 米德列斯公司 用于生产人类抗体的转基因转染色体啮齿动物
GB0110029D0 (en) 2001-04-24 2001-06-13 Grosveld Frank Transgenic animal
US20060073141A1 (en) 2001-06-28 2006-04-06 Domantis Limited Compositions and methods for treating inflammatory disorders
EP1423510A4 (en) 2001-08-03 2005-06-01 Glycart Biotechnology Ag ANTIBODY GLYCOSYLATION VARIANTS WITH INCREASED CELL CYTOTOXICITY DEPENDENT OF ANTIBODIES
ES2337986T3 (es) 2001-08-10 2010-05-03 Aberdeen University Dominios de union de antigenos de peces.
US7371849B2 (en) 2001-09-13 2008-05-13 Institute For Antibodies Co., Ltd. Methods of constructing camel antibody libraries
JP2005289809A (ja) 2001-10-24 2005-10-20 Vlaams Interuniversitair Inst Voor Biotechnologie Vzw (Vib Vzw) 突然変異重鎖抗体
ES2326964T3 (es) 2001-10-25 2009-10-22 Genentech, Inc. Composiciones de glicoproteina.
CN1610696A (zh) * 2001-12-20 2005-04-27 人体基因组科学有限公司 免疫特异性结合trail受体的抗体
US20040093621A1 (en) 2001-12-25 2004-05-13 Kyowa Hakko Kogyo Co., Ltd Antibody composition which specifically binds to CD20
US7745140B2 (en) 2002-01-03 2010-06-29 The Trustees Of The University Of Pennsylvania Activation and expansion of T-cells using an engineered multivalent signaling platform as a research tool
BR0309145A (pt) 2002-04-09 2005-02-01 Kyowa Hakko Kogyo Kk Células das quais o genoma é modificado
WO2003085119A1 (fr) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Procede d'amelioration de l'activite d'une composition d'anticorps de liaison avec le recepteur fc$g(g) iiia
CA2481920A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Antibody composition-containing medicament
ATE503829T1 (de) 2002-04-09 2011-04-15 Kyowa Hakko Kirin Co Ltd Zelle mit erniedrigter oder deletierter aktivität eines am gdp-fucosetransport beteiligten proteins
CA2481837A1 (en) 2002-04-09 2003-10-16 Kyowa Hakko Kogyo Co., Ltd. Production process for antibody composition
AU2003236019A1 (en) 2002-04-09 2003-10-20 Kyowa Hakko Kirin Co., Ltd. Drug containing antibody composition appropriate for patient suffering from Fc Gamma RIIIa polymorphism
AU2003239966B9 (en) 2002-06-03 2010-08-26 Genentech, Inc. Synthetic antibody phage libraries
US7361740B2 (en) 2002-10-15 2008-04-22 Pdl Biopharma, Inc. Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis
GB0228210D0 (en) 2002-12-03 2003-01-08 Babraham Inst Single chain antibodies
PL212899B1 (pl) 2002-12-16 2012-12-31 Genentech Inc Humanizowane przeciwcialo, kompozycja zawierajaca to przeciwcialo, wyrób fabryczny, przeciwcialo lub jego fragment do zastosowania w sposobie indukowania apoptozy, izolowany kwas nukleinowy, wektor ekspresji, komórka gospodarza, sposób wytwarzania przeciwciala lub jego fragmentu, plynny preparat i zastosowanie przeciwciala do wytwarzania leku
EP1585767A2 (en) 2003-01-16 2005-10-19 Genentech, Inc. Synthetic antibody phage libraries
CA2542046A1 (en) 2003-10-08 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Fused protein composition
CA2542125A1 (en) 2003-10-09 2005-04-21 Kyowa Hakko Kogyo Co., Ltd. Process for producing antibody composition by using rna inhibiting the function of .alpha.1,6-fucosyltransferase
HUE031632T2 (en) 2003-11-05 2017-07-28 Roche Glycart Ag Antigen binding molecules with enhanced Fc receptor binding affinity and effector function
BR122018071808B8 (pt) 2003-11-06 2020-06-30 Seattle Genetics Inc conjugado
JPWO2005053742A1 (ja) 2003-12-04 2007-06-28 協和醗酵工業株式会社 抗体組成物を含有する医薬
JP5128935B2 (ja) 2004-03-31 2013-01-23 ジェネンテック， インコーポレイテッド ヒト化抗ＴＧＦ−β抗体
US7785903B2 (en) 2004-04-09 2010-08-31 Genentech, Inc. Variable domain library and uses
EP2360186B1 (en) 2004-04-13 2017-08-30 F. Hoffmann-La Roche AG Anti-P-selectin antibodies
WO2005118788A2 (en) 2004-05-27 2005-12-15 The Trustees Of The University Of Pennsylvania Novel artificial antigen presenting cells and uses therefor
SI1776383T1 (sl) 2004-07-22 2014-12-31 Erasmus University Medical Center Rotterdam Department of Cell Biology and Genetics Vezavne molekule
US7563443B2 (en) 2004-09-17 2009-07-21 Domantis Limited Monovalent anti-CD40L antibody polypeptides and compositions thereof
TWI309240B (en) 2004-09-17 2009-05-01 Hoffmann La Roche Anti-ox40l antibodies
NZ580115A (en) 2004-09-23 2010-10-29 Genentech Inc Cysteine engineered antibody light chains and conjugates
EP1957531B1 (en) 2005-11-07 2016-04-13 Genentech, Inc. Binding polypeptides with diversified and consensus vh/vl hypervariable sequences
EP1973951A2 (en) 2005-12-02 2008-10-01 Genentech, Inc. Binding polypeptides with restricted diversity sequences
CA2638117A1 (en) 2006-01-25 2007-08-30 Erasmus University Medical Center Rotterdam Generation of heavy-chain only antibodies in transgenic animals
TW200812616A (en) 2006-05-09 2008-03-16 Genentech Inc Binding polypeptides with optimized scaffolds
US20100166734A1 (en) 2006-12-20 2010-07-01 Edward Dolk Oral delivery of polypeptides
US20080226635A1 (en) 2006-12-22 2008-09-18 Hans Koll Antibodies against insulin-like growth factor I receptor and uses thereof
CN100592373C (zh) 2007-05-25 2010-02-24 群康科技(深圳)有限公司 液晶显示面板驱动装置及其驱动方法
RU2567151C2 (ru) * 2007-06-12 2015-11-10 Ац Иммуне С.А. Гуманизированные антитела к амилоиду бета
AU2008328779B2 (en) 2007-11-27 2014-06-05 Ablynx N.V. Amino acid sequences directed against HER2 and polypeptides comprising the same for the treatment of cancers and/or tumors
US8592562B2 (en) 2008-01-07 2013-11-26 Amgen Inc. Method for making antibody Fc-heterodimeric molecules using electrostatic steering effects
CN101550416B (zh) * 2008-03-18 2012-01-25 陈志南 人源化单抗Hu-ScFv18的轻、重链可变区基因和其编码多肽及其应用
US20100122358A1 (en) 2008-06-06 2010-05-13 Crescendo Biologics Limited H-Chain-only antibodies
DK2509409T3 (en) 2009-12-10 2016-11-14 Regeneron Pharma MICE, WHICH PRODUCES HEAVY CHAIN ANTIBODIES
PT2580243T (pt) * 2010-06-09 2020-01-22 Genmab As Anticorpos contra cd38 humana
NZ607480A (en) 2010-08-03 2014-10-31 Abbott Lab Dual variable domain immunoglobulins and uses thereof
HUE047507T2 (hu) 2011-10-17 2020-04-28 Massachusetts Inst Technology Intracelluláris célbajuttatás
TWI679212B (zh) 2011-11-15 2019-12-11 美商安進股份有限公司 針對ｂｃｍａ之e3以及ｃｄ３的結合分子
EP3594245A1 (en) * 2012-02-13 2020-01-15 Seattle Children's Hospital d/b/a Seattle Children's Research Institute Bispecific chimeric antigen receptors and therapeutic uses thereof
ES2959443T3 (es) 2012-02-22 2024-02-26 Univ Pennsylvania Uso del dominio de señalización de CD2 en receptores de antígenos quiméricos de segunda generación
EA201990959A1 (ru) 2012-04-11 2020-02-10 Дзе Юнайтед Стейтс Оф Америка, Эз Репрезентед Бай Дзе Секретари, Департмент Оф Хелс Энд Хьюман Сёрвисез Химерные антигенные рецепторы, нацеленные на антиген созревания b-клеток
EP2904106A4 (en) * 2012-10-01 2016-05-11 Univ Pennsylvania COMPOSITIONS AND METHODS FOR TARGETING STROMAL CELLS FOR THE TREATMENT OF CANCER
TW201425336A (zh) 2012-12-07 2014-07-01 Amgen Inc Ｂｃｍａ抗原結合蛋白質
US9243058B2 (en) * 2012-12-07 2016-01-26 Amgen, Inc. BCMA antigen binding proteins
EP2953972B1 (en) * 2013-02-05 2020-07-08 EngMab Sàrl Method for the selection of antibodies against bcma
CN104045713B (zh) * 2013-03-13 2019-02-12 江苏诺迈博生物医药科技有限公司 一种抗Blys的单克隆抗体及含有该抗体的药物组合物
UY35468A (es) * 2013-03-16 2014-10-31 Novartis Ag Tratamiento de cáncer utilizando un receptor quimérico de antígeno anti-cd19
AU2014248119B2 (en) * 2013-04-03 2019-06-20 Memorial Sloan-Kettering Cancer Center Effective generation of tumor-targeted T-cells derived from pluripotent stem cells
GB201317929D0 (en) 2013-10-10 2013-11-27 Ucl Business Plc Chimeric antigen receptor
WO2015120187A1 (en) 2014-02-05 2015-08-13 The University Of Chicago Chimeric antigen receptors recognizing cancer-spevific tn glycopeptide variants
EP3119423B1 (en) 2014-03-15 2022-12-14 Novartis AG Treatment of cancer using chimeric antigen receptor
BR112016021572A2 (pt) 2014-03-21 2017-10-03 Regeneron Pharma Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação
EP3172237A2 (en) 2014-07-21 2017-05-31 Novartis AG Treatment of cancer using humanized anti-bcma chimeric antigen receptor
EP3172231B1 (en) 2014-07-24 2021-05-05 Bluebird Bio, Inc. Bcma chimeric antigen receptors
KR102317315B1 (ko) * 2014-08-04 2021-10-27 에프. 호프만-라 로슈 아게 이중특이적 t 세포 활성화 항원 결합 분자
EP3029067A1 (en) 2014-12-01 2016-06-08 Deutsches Krebsforschungszentrum Use of blocking-reagents for reducing unspecific T cell-activation
ES2750725T3 (es) 2014-12-12 2020-03-26 Bluebird Bio Inc Receptores de antígeno quiméricos BCMA
EP3325613A4 (en) 2015-07-20 2018-12-19 Angiocrine Bioscience, Inc. Engineered endothelial cells expressing an ets transcription factor
CN105384825B (zh) 2015-08-11 2018-06-01 南京传奇生物科技有限公司 一种基于单域抗体的双特异性嵌合抗原受体及其应用
CN105777911B (zh) 2016-04-12 2019-07-02 上海优卡迪生物医药科技有限公司 抗bcma嵌合抗原受体、编码基因、重组表达载体及其构建方法和应用
CN108395481B (zh) 2017-02-08 2021-02-05 西比曼生物科技（香港）有限公司 一种靶向cd20的car的构建及其工程化t细胞的活性鉴定
CA3057265A1 (en) 2017-04-19 2018-10-25 Allogene Therapeutics, Inc. Improved t cell compositions and methods
WO2019000223A1 (en) 2017-06-27 2019-01-03 Nanjing Legend Biotech Co., Ltd. ENABLERS OF IMMUNE EFFECTOR CELLS OF CHIMERIC ANTIBODIES AND METHODS OF USE THEREOF
CN109306014B (zh) 2017-07-27 2022-04-12 上海细胞治疗研究院 一种靶向间皮素的嵌合抗原受体修饰t细胞及其用途
WO2019133969A2 (en) 2017-12-29 2019-07-04 Memorial Sloan-Kettering Cancer Center Enhanced chimeric antigen receptors and uses thereof
US20210023170A1 (en) 2018-02-12 2021-01-28 University Of Florida Research Foundation, Incorporated Fviii chimeric antigen receptor tregs for tolerance induction in hemophilia a
EP4022041A4 (en) 2019-08-28 2023-11-22 Legend Biotech USA Inc. NEF-CONTAINING T CELLS AND METHODS OF PRODUCTION THEREOF
US20230058669A1 (en) 2019-12-16 2023-02-23 Nanjing Legend Biotech Co., Ltd. Single domain antibodies and chimeric antigen receptors targeting bcma and methods of use thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104583230A (zh) * 2012-07-13 2015-04-29 宾夕法尼亚大学董事会 通过共同引入双特异性抗体增强car t细胞的活性

Also Published As

Publication number Publication date
CN109311999A (zh) 2019-02-05
KR20240017408A (ko) 2024-02-07
EA201890302A1 (ru) 2018-10-31
CN109153731B (zh) 2021-04-02
PH12019500193A1 (en) 2019-07-29
CA3019453A1 (en) 2018-02-15
CN105384825A (zh) 2016-03-09
SG11201900635QA (en) 2019-02-27
CN113234173A (zh) 2021-08-10
CN113185616A (zh) 2021-07-30
EA201990208A1 (ru) 2019-07-31
UA126441C2 (uk) 2022-10-05
JP7168173B2 (ja) 2022-11-09
KR20230052294A (ko) 2023-04-19
PH12018500295A1 (en) 2021-05-10
SA518390904B1 (ar) 2023-02-22
EP4282877A2 (en) 2023-11-29
EP3334765A4 (en) 2019-05-08
AU2020200151C1 (en) 2022-09-08
CA2994579C (en) 2023-07-11
CA3189388A1 (en) 2018-02-15
US10934363B2 (en) 2021-03-02
EP3475307A4 (en) 2020-08-19
HRP20231542T1 (hr) 2024-03-15
CL2019000326A1 (es) 2019-10-04
CL2021001706A1 (es) 2022-01-28
CR20210042A (es) 2021-02-26
AU2022204180A1 (en) 2022-07-07
WO2018028647A1 (en) 2018-02-15
US20210163615A1 (en) 2021-06-03
EP4282877A3 (en) 2024-02-21
EP3896091A1 (en) 2021-10-20
CN113234174B (zh) 2024-01-09
CN117756941A (zh) 2024-03-26
JP2021087455A (ja) 2021-06-10
EP3896091B1 (en) 2023-09-27
KR20180035918A (ko) 2018-04-06
CN113234173B (zh) 2022-03-11
MY192392A (en) 2022-08-18
BR112019002687A2 (pt) 2019-05-14
CN113185616B (zh) 2024-03-01
EP3475307A1 (en) 2019-05-01
RS64925B1 (sr) 2023-12-29
SI3896091T1 (sl) 2024-03-29
AU2021200453C1 (en) 2023-11-16
NZ750366A (en) 2022-10-28
JP2018525033A (ja) 2018-09-06
CO2018001405A2 (es) 2018-11-22
MY188362A (en) 2021-12-03
EP3334765A1 (en) 2018-06-20
CL2021001686A1 (es) 2022-01-28
US11186647B2 (en) 2021-11-30
CN113185615A (zh) 2021-07-30
EP4282878A3 (en) 2024-03-06
CR20190050A (es) 2019-06-11
BR112018002844A2 (pt) 2019-04-30
SG10201913485QA (en) 2020-02-27
EP4063397A1 (en) 2022-09-28
CR20180153A (es) 2018-08-09
KR102512934B1 (ko) 2023-03-23
AU2020200151B2 (en) 2022-03-17
CL2018000378A1 (es) 2018-08-17
US20200078399A1 (en) 2020-03-12
CN113234174A (zh) 2021-08-10
AU2017311089B2 (en) 2020-11-19
IL294683A (en) 2022-09-01
CA2994579A1 (en) 2017-02-16
IL264607A (en) 2019-02-28
CA3019453C (en) 2023-04-04
PT3896091T (pt) 2023-11-29
JP2019527557A (ja) 2019-10-03
AU2017311089A1 (en) 2019-02-21
JP2022183283A (ja) 2022-12-08
MX2022015823A (es) 2023-01-24
MX2018001739A (es) 2018-08-15
AU2016305075A1 (en) 2018-03-08
JP2023024810A (ja) 2023-02-16
JP2024032975A (ja) 2024-03-12
MX2019001294A (es) 2019-04-25
DK3896091T3 (da) 2023-12-11
US20180230225A1 (en) 2018-08-16
EP4282878A2 (en) 2023-11-29
AU2016305075B2 (en) 2019-10-10
US11535677B2 (en) 2022-12-27
AU2021200453B2 (en) 2023-03-30
LT3896091T (lt) 2023-12-27
ZA201807836B (en) 2019-08-28
IL257297B (en) 2022-08-01
JP6851461B2 (ja) 2021-03-31
KR20240014108A (ko) 2024-01-31
KR20190065999A (ko) 2019-06-12
UA125818C2 (uk) 2022-06-15
US20210261675A1 (en) 2021-08-26
CN109153731A (zh) 2019-01-04
CO2019000946A2 (es) 2019-02-08
JP2021094037A (ja) 2021-06-24
WO2017025038A1 (en) 2017-02-16
ZA201800703B (en) 2018-12-19
AU2021200453A1 (en) 2021-02-25
IL257297A (en) 2018-03-29
FI3896091T3 (fi) 2023-12-04
HUE064534T2 (hu) 2024-03-28
US20220127371A1 (en) 2022-04-28
CR20210225A (es) 2021-06-24
JP6859347B2 (ja) 2021-04-14
AU2020200151A1 (en) 2020-01-30

Similar Documents

Publication Publication Date Title
CN105384825B (zh) 一种基于单域抗体的双特异性嵌合抗原受体及其应用
CN107880128B (zh) 一种抗cd19的全人源抗体或抗体片段及其方法和应用
RU2748281C2 (ru) Полностью человеческие антитела к мезотелину и иммунные эффекторные клетки, нацеленные на мезотелин
JP6753945B2 (ja) 抗人ｐｄ−ｌ１人源化単クローン抗体及び応用
US11713348B2 (en) ScFv amino acid sequence, chimeric antigen receptor containing same and application thereof
CN109134665A (zh) 一种基于单域抗体的bcma嵌合抗原受体及应用
JP2019532625A5 (zh)
AU2016295601B2 (en) Tumor-specific anti-EGFR antibody and application thereof
CN107428832A (zh) 抗pd‑l1抗体
WO2015197016A1 (zh) 时空可调性抑制病理性靶细胞的***
CN109942708B (zh) 一种抗bcma的单域抗体及其应用
CN108164600B (zh) 一种抗gpc3抗体及其制备方法和用途
CN103833852A (zh) 针对磷脂酰肌醇蛋白多糖-3和t细胞抗原的双特异性抗体
US20220332829A1 (en) Anti-b7-h3 antibody and application thereof
CN104774268A (zh) 一种双特异性抗体egfr×cd3的构建及应用
CN107141356A (zh) 一种光诱导二聚体型嵌合抗原受体
CN104829727B (zh) 一种双特异性抗体cd19×cd3的构建及应用
CN111303287B (zh) 一种anti-CD19的全人源抗体或抗体片段及其嵌合抗原受体和应用
CN113501879B (zh) 一种解除肿瘤免疫微环境中免疫抑制的双功能抗体及其应用和制备方法
CN108383908A (zh) 识别人源ctla-4并阻断其功能的全人源单克隆抗体或抗体片段及其制备方法和用途
CN110229230A (zh) 一种靶向cd38的单域抗体及其应用
CN102732974A (zh) 噬菌体抗体库的构建方法及应用此库筛选到的抗cd6抗体
WO2023273595A1 (zh) 一种结合trop2的抗体及靶向trop2和cd3的双特异性抗体及其制备方法与应用
US20230399412A1 (en) Antibody and chimeric antigen receptor (car) binding to cd70, and application thereof
CN115151572A (zh) 针对ror1的抗体及其用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant