HRP20230239T1 - Polipeptidi koji reagiraju na transformirajući faktor rasta – beta i postupci za njihovu upotrebu - Google Patents

Polipeptidi koji reagiraju na transformirajući faktor rasta – beta i postupci za njihovu upotrebu Download PDF

Info

Publication number
HRP20230239T1
HRP20230239T1 HRP20230239TT HRP20230239T HRP20230239T1 HR P20230239 T1 HRP20230239 T1 HR P20230239T1 HR P20230239T T HRP20230239T T HR P20230239TT HR P20230239 T HRP20230239 T HR P20230239T HR P20230239 T1 HRP20230239 T1 HR P20230239T1
Authority
HR
Croatia
Prior art keywords
optionally
cell
seq
cells
region
Prior art date
Application number
HRP20230239TT
Other languages
English (en)
Inventor
Yvonne Yu-Hsua Chen
ZeNan Li CHANG
Original Assignee
The Regents Of The University Of California
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 The Regents Of The University Of California filed Critical The Regents Of The University Of California
Publication of HRP20230239T1 publication Critical patent/HRP20230239T1/hr

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
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • 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
    • C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
    • 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
    • A61K39/0005—Vertebrate antigens
    • A61K39/0008—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
    • 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
    • A61K39/462—Cellular immunotherapy characterized by the effect or the function of the cells
    • A61K39/4621—Cellular immunotherapy characterized by the effect or the function of the cells immunosuppressive or immunotolerising
    • 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
    • A61K39/46433—Antigens related to auto-immune diseases; Preparations to induce self-tolerance
    • 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
    • A61K39/46443—Growth factors
    • A61K39/464434—Transforming growth factor [TGF]
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/70521—CD28, CD152
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2863—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for growth factors, growth regulators
    • 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
    • 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
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0634—Cells from the blood or the immune system
    • C12N5/0636—T lymphocytes
    • C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5044—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics involving specific cell types
    • G01N33/5047—Cells of the immune system
    • G01N33/505—Cells of the immune system involving T-cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/515—Animal cells
    • A61K2039/5158—Antigen-pulsed cells, e.g. T-cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/52—Constant or Fc region; Isotype
    • C07K2317/53—Hinge
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • 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
    • C07K2317/60—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
    • C07K2317/624—Disulfide-stabilized antibody (dsFv)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/33—Fusion polypeptide fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
    • C—CHEMISTRY; METALLURGY
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/10—Growth factors
    • C12N2501/15—Transforming growth factor beta (TGF-β)
    • 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
    • C12N2501/00—Active agents used in cell culture processes, e.g. differentation
    • C12N2501/20—Cytokines; Chemokines
    • C12N2501/23—Interleukins [IL]
    • C12N2501/2302—Interleukin-2 (IL-2)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biomedical Technology (AREA)
  • Genetics & Genomics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Mycology (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Hematology (AREA)
  • General Engineering & Computer Science (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oncology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)

Claims (15)

1. Kimerni antigenski receptor (CAR) koji sadrži signalni peptid, domena za vezanje antigena TGF-β s varijabilnom teškom (VH) i varijabilnom lakom (VL) regijom antitijela, peptidnu razmaknicu, transmembransku domenu, i endodomenu koja emitira aktivacijski signal T stanicama nakon vezanja antigena; pri čemu se domena za vezanje antigena TGF-β specifično veže za rastvorni TGF-β i pri čemu: (a) VH regija sadrži SEQ ID NO:5 kao HCDR1, SEQ ID NO:6 kao HCDR2; i SEQ ID NO:7 kao HCDR3 i VL regija sadrži SEQ ID NO:8 kao LCDR1, SEQ ID NO:9 kao LCDR2; i SEQ ID NO:10 kao LCDR3; ili (b) VH regija sadrži SEQ ID NO:11 kao HCDR1, SEQ ID NO:12 kao HCDR2; i SEQ ID NO: 13 kao HCDR3 i VL regija sadrži SEQ ID NO:14 kao LCDR1, SEQ ID NO:15 kao LCDR2; i SEQ ID NO:16 kao LCDR3; ili (c) VH regija sadrži SEQ ID NO:21 kao HCDR1, SEQ ID NO:22 kao HCDR2; i SEQ ID NO:23 kao HCDR3 i VL regija sadrži SEQ ID NO:24 kao LCDR1, SEQ ID NO:25 kao LCDR2; i SEQ ID NO:26 kao LCDR3; i pri čemu CAR ima strukturu: S-X-PL-Y-PS-T-E ili S-Y-PL-X-PS-T-E pri čemu je S signalni peptid, X je VH, PL je peptidni povezivač, Y je VL, PS je peptidna razmaknica, T je transmembranska domena, i E je endodomena.
2. CAR prema patentnom zahtjevu 1(a), pri čemu VH regija sadrži SEQ ID NO:1 i VL regija sadrži SEQ ID NO:2.
3. CAR prema patentnom zahtjevu 1, pri čemu: (a) VH regija prema patentnom zahtjevu 1(b) sadrži SEQ ID NO:3 i VL regija sadrži SEQ ID NO:4; ili (b) VH regija prema patentnom zahtjevu 1(c) sadrži SEQ ID NO: 19 i VL regija sadrži SEQ ID NO:20.
4. CAR prema bilo kojem od patentnih zahtjeva 1–3, pri čemu: (a) VH regija i VL regija su odvojene pomoću peptidnog povezivača; i/ili (b) CAR dalje sadrži kostimulatornu regiju, opcionalno pri čemu je kostimulatorna regija između transmembranske domene i endodomene; i/ili (c) transmembranska domena sadrži transmembransku domenu iz CD28; i/ili (d) endodomena sadrži CD28 ili CD3 zeta signalnu domenu; pri čemu je opcionalno peptidni povezivač glicin-serinski povezivač.
5. CAR prema bilo kojem od patentnih zahtjeva 1(b), 1(c), 2, 3 ili 4, pri čemu je peptidni povezivač najmanje 4 aminokiseline.
6. CAR prema bilo kojem od patentnih zahtjeva 1–5, pri čemu: (a) endodomena je CD3-zeta signalna domena; i/ili (b) peptidna razmaknica sadrži: (i) manje od 50 aminokiselina; ili (ii) više od 50 aminokiselina; i/ili (c) peptidna razmaknica sadrži zglobnu regiju molekula IgG; i/ili (d) peptidna razmaknica sadrži zglobnu regiju i regiju CH2CH3 molekula IgG, pri čemu se opcionalno peptidna razmaknica sastoji od zglobne regije molekula IgG; i/ili (e) CAR dalje sadrži peptid za detekciju, pri čemu je opcionalno peptid za detekciju peptid iz SEQ ID NO:17, 94, ili 95: i opcionalno: (i) peptid za detekciju je okružen povezivačima; i/ili (ii) peptid za detekciju je N-terminalni za VH i VL regije; i/ili (iii) peptid za detekciju je između signalnog peptida i domene za vezanje antigena.
7. CAR prema bilo kojem od patentnih zahtjeva 1–6, pri čemu: (a) signalni peptid sadrži SEQ ID NO:18; i/ili (b) CAR dalje sadrži domenu za vezivanje antigena specifičnu za molekulu raka, pri čemu opcionalno molekula raka sadrži Her2 ili sadrži CD19 ili CD20; ili (c) CAR dalje sadrži domenu za vezivanje antigena specifičnu za molekulu raka, pri čemu se opcionalno domena za vezivanje antigena specifična za molekulu raka veže za CAIX, CD33, CD44v7/8, CEA, EGP-2, EGP-40, erb-B2, erbB3, erb-B4, FBP, fetalni acetiholinski receptor, GD2, GD3, Her2/neu, IL-13Ralpha2, KDR, k-laki lanac, LeY, L1 molekula stanične adhezije, MAGE-A1, mezotelin, MUC1, NKG2D ligande, onkofetalni antigen (h5T4), PSCA, PSMA, TAA koji su ciljni za mAb IgE, TAG-72, ili VEGF-R2.
8. Izolirana nukleinska kiselina koja kodira CAR prema bilo kojem od patentnih zahtjeva 1–7.
9. Stanica koja sadrži CAR prema bilo kojem od patentnih zahtjeva 1–7 ili nukleinska kiselina prema patentnom zahtjevu 8, pri čemu: (A) opcionalno stanica dalje sadrži kimerni antigenski receptor (CAR) specifičan za rak, i opcionalno se CAR specifičan za rak specifično veže za: (i) Her2 ili (ii) specifično veže za CD19 ili CD20, pri čemu opcionalno stanica je imunološka stanica; i (B) opcionalno: (a) stanica je T stanica, opcionalno CD4+ ili CD8+ T stanica; ili T regulatorna stanica; ili (b) stanica je stanica prirodni ubojica.
10. Stanica prema patentnom zahtjevu 9 za upotrebu u postupku za stimuliranje imunološkog odgovora, pri čemu navedeni postupak obuhvaća dovođenje u kontakt stanice prema patentnom zahtjevu 9 sa TGF-β, pri čemu opcionalno: (i) stimuliranje imunološkog odgovora obuhvaća povećanje ekspresije i/ili lučenja imunostimulirajućih citokina i/ili molekula, pri čemu su opcionalno imunostimulirajući citokini i/ili molekule jedan ili više od TNF-α, IFN-β, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18 i faktora stimulacije kolonije granulocitnih makrofaga; ili (ii) stimuliranje imunološkog odgovora koji obuhvaća povećanje proliferacije imunoloških stanica, opcionalno pri čemu imunološke stanice su T stanice.
11. Stanica prema patentnom zahtjevu 9 za upotrebu u postupku za stimuliranje imunološkog odgovora, pri čemu navedeni postupak obuhvaća dovođenje u kontakt stanice prema patentnom zahtjevu 9 ili patentnom zahtjevu 10 sa TGF-β, pri čemu stanica je in vivo u subjektu kojem je potrebna imunološka stimulacija i opcionalno TGF-β je endogeni TGF-β proizveden u subjektu kome je potrebna imunološka stimulacija, pri čemu opcionalno: (i) ljudski subjekt ima rak, fibrozu, ili otvorenu ranu, pri čemu opcionalno rak je melanom; (ii) ljudski subjekt ima malignitet B-stanica; ili (iii) ljudski subjekt ima čvrsti tumor; i pri čemu opcionalno: (iv) postupak dalje obuhvaća davanje stanice ljudskom subjektu; i/ili (v) postupak dalje obuhvaća davanje TGF-β subjektu.
12. Ex vivo postupak za detektiranje TGF-β u otopini koja obuhvaća dovođenje u kontakt stanica prema patentnom zahtjevu 9 s otopinom i mjerenje imunološke stimulacije; pri čemu povećanje u imunološkoj stimulaciji ukazuje na prisutstvo TGF-β i odsustvo povećanja u imunološkoj stimulaciji ukazuje na odsustvo TGF-β, pri čemu opcionalno: (i) imunološka stimulacija obuhvaća ekspresiju imunostimulirajućih citokina i/ili molekula, pri čemu opcionalno imunostimulirajući citokini i/ili molekule su jedan ili više od TNF-α, IFN-β, IFN-γ, IL-1, IL2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-18 i faktora stimulacije kolonije granulocitnih makrofaga; ili (ii) imunološka stimulacija obuhvaća povećanje u proliferaciji imunoloških stanica, pri čemu opcionalno imunološke stanice su T stanice.
13. Postupak za dobivanje CAR prema bilo kojem od patentnih zahtjeva 1–7 koji obuhvaća eksprimiranje nukleotida koji kodira CAR u stanici.
14. Postupak za umnožavanje T stanica in vitro, pri čemu postupak obuhvaća dovođenje u kontakt T stanice prema patentnom zahtjevu 9B s sastavom koji sadrži TGF-β, pri čemu opcionalno sastav: (a) sadrži 1–50 ng/mL TGF-β; i/ili (b) sadrži IL-2 i opcionalno sastav sadrži 20–400 U/mL IL-2, pri čemu opcionalno: (a) (i) postupak dalje obuhvaća dovođenje u kontakt stanica s hraniteljskim stanicama, pri čemu opcionalno hraniteljske stanice su ozračene; ili (ii) postupak isključuje kontakt T stanica s hraniteljskim stanicama; i/ili (b) T stanica je regulatorna T stanica, pri čemu opcionalno umnožene regulatorne T stanice sadrže manje od 10% neregulatornih T stanica.
15. Stanica prema patentnom zahtjevu 9B za upotrebu u postupku za liječenje bolesti ili patološkog stanja kod pacijenta, pri čemu opcionalno: (a) stanica je regulatorna T stanica, pri čemu opcionalno bolest je: autoimuna bolest; ili (b) bolest je rak; pri čemu opcionalno postupak dalje obuhvaća umnožavanje stanica in vitro postupkom koji obuhvaća dovođenje u kontakt stanice in vitro s sastavom koji sadrži TGF-β; pri čemu opcionalno: (a) sastav sadrži 1–50 ng/mL TGF-β; i/ili (b) sastav dalje sadrži IL-2, i opcionalno sastav sadrži 20–400 U/mL IL-2; pri čemu opcionalno: (a) postupak dalje obuhvaća dovođenje u kontakt stanica s hraniteljskim stanicama, pri čemu opcionalno hraniteljske stanice su ozračene; ili (b) postupak isključuje kontakt T stanica s hraniteljskim stanicama; pri čemu opcionalno T stanica je regulatorna T stanica, pri čemu opcionalno umnožene regulatorne T stanice sadrže manje od 10% neregulatornih T stanica; pri čemu opcionalno autoimuna bolest je reumatoidni artritis; i pri čemu opcionalno postupak dalje obuhvaća davanje TGF-β pacijentu.
HRP20230239TT 2015-10-30 2016-10-28 Polipeptidi koji reagiraju na transformirajući faktor rasta – beta i postupci za njihovu upotrebu HRP20230239T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201562248685P 2015-10-30 2015-10-30
PCT/US2016/059444 WO2017075433A1 (en) 2015-10-30 2016-10-28 Transforming growth factor-beta-responsive polypeptides and their methods for use
EP16860930.3A EP3368571B1 (en) 2015-10-30 2016-10-28 Transforming growth factor-beta-responsive polypeptides and their methods for use

Publications (1)

Publication Number Publication Date
HRP20230239T1 true HRP20230239T1 (hr) 2023-04-14

Family

ID=58631218

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20230239TT HRP20230239T1 (hr) 2015-10-30 2016-10-28 Polipeptidi koji reagiraju na transformirajući faktor rasta – beta i postupci za njihovu upotrebu

Country Status (16)

Country Link
US (2) US11014980B2 (hr)
EP (2) EP3368571B1 (hr)
JP (2) JP7104624B2 (hr)
KR (1) KR20180092947A (hr)
CN (2) CN108884155B (hr)
DK (1) DK3368571T3 (hr)
ES (1) ES2935372T3 (hr)
FI (1) FI3368571T3 (hr)
HR (1) HRP20230239T1 (hr)
HU (1) HUE061424T2 (hr)
LT (1) LT3368571T (hr)
PL (1) PL3368571T3 (hr)
PT (1) PT3368571T (hr)
RS (1) RS64053B1 (hr)
SI (1) SI3368571T1 (hr)
WO (1) WO2017075433A1 (hr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2971186A1 (en) 2014-12-15 2016-06-23 The Regents Of The University Of California Cytotoxic molecules responsive to intracellular ligands for selective t cell mediated killing
RS64053B1 (sr) * 2015-10-30 2023-04-28 Univ California Polipeptidi koji reaguju na transformišući faktor rasta – beta i postupci za njihovu upotrebu
AU2017247796A1 (en) * 2016-04-05 2018-09-27 Glaxosmithkline Intellectual Property Development Limited Inhibition of TGFBeta in immunotherapy
US11701384B2 (en) 2016-09-02 2023-07-18 The Regents Of The University Of California Methods and compositions involving interleukin-6 receptor alpha-binding single chain variable fragments
EP3646878A4 (en) * 2017-06-30 2021-03-24 Kolon Life Science, Inc. PHARMACEUTICAL COMPOSITION FOR THE PREVENTION OR TREATMENT OF OSTEOARTHRITIS
CN109486745A (zh) * 2017-09-12 2019-03-19 中国人民解放军第三军医大学第附属医院 Fg-4592在促进表皮干细胞迁移方面的应用
CA3088832A1 (en) * 2018-01-19 2019-07-25 Miltenyi Biotec B.V. & Co. KG Regulatory t cell expressing a chimeric antigen receptor
GB201807693D0 (en) * 2018-05-11 2018-06-27 Autolus Ltd Cell
EP3773918A4 (en) 2019-03-05 2022-01-05 Nkarta, Inc. CD19 DIRECTED CHIMERIC ANTIGEN RECEPTORS AND THEIR USES IN IMMUNOTHERAPY
CN111748043B (zh) * 2020-07-03 2022-09-02 深圳市体内生物医药科技有限公司 一种嵌合抗原受体及其应用
CN112500491B (zh) * 2020-12-18 2022-04-08 深圳市迈加瑞生物技术有限公司 一种特异性中和辅助性T细胞TGF-β信号的双特异性抗体、其药物组合及其用途
WO2023023602A1 (en) * 2021-08-19 2023-02-23 Boan Boston Llc Fusion proteins for dephosphorylating proteins that regulate t cell activation through the tcr signaling pathway
WO2023201206A1 (en) * 2022-04-11 2023-10-19 The Board Of Trustees Of The Leland Stanford Junior University Cytokine adaptor proteins and uses thereof

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0154316B1 (en) 1984-03-06 1989-09-13 Takeda Chemical Industries, Ltd. Chemically modified lymphokine and production thereof
US5677425A (en) 1987-09-04 1997-10-14 Celltech Therapeutics Limited Recombinant antibody
GB8725529D0 (en) 1987-10-30 1987-12-02 Delta Biotechnology Ltd Polypeptides
CA2006596C (en) 1988-12-22 2000-09-05 Rika Ishikawa Chemically-modified g-csf
SE509359C2 (sv) 1989-08-01 1999-01-18 Cemu Bioteknik Ab Användning av stabiliserade protein- eller peptidkonjugat för framställning av ett läkemedel
US5503978A (en) 1990-06-11 1996-04-02 University Research Corporation Method for identification of high affinity DNA ligands of HIV-1 reverse transcriptase
US5580737A (en) 1990-06-11 1996-12-03 Nexstar Pharmaceuticals, Inc. High-affinity nucleic acid ligands that discriminate between theophylline and caffeine
US5543293A (en) 1990-06-11 1996-08-06 Nexstar Pharmaceuticals, Inc. DNA ligands of thrombin
US5714350A (en) 1992-03-09 1998-02-03 Protein Design Labs, Inc. Increasing antibody affinity by altering glycosylation in the immunoglobulin variable region
US5631146A (en) 1995-01-19 1997-05-20 The General Hospital Corporation DNA aptamers and catalysts that bind adenosine or adenosine-5'-phosphates and methods for isolation thereof
WO1998050432A1 (en) 1997-05-07 1998-11-12 Bristol-Myers Squibb Company Recombinant antibody-enzyme fusion proteins
US6492497B1 (en) * 1999-04-30 2002-12-10 Cambridge Antibody Technology Limited Specific binding members for TGFbeta1
US7066469B2 (en) 2002-08-06 2006-06-27 University of Kentucky Research Foundation Board of Supervisors of Louisiana State University Seal assembly for machinery housing
UA80296C2 (en) 2002-09-06 2007-09-10 Biogen Inc Imidazolopyridines and methods of making and using the same
WO2005000200A2 (en) * 2003-05-09 2005-01-06 Sugen, Inc. Novel kinases
RU2006120483A (ru) 2003-11-13 2007-12-20 Дженентек, Инк. (Us) Скрининг-анализы и способы лечения опухоли
ZA200608130B (en) 2004-03-31 2008-12-31 Genentech Inc Humanized anti-TGF-beta antibodies
WO2006046661A1 (ja) 2004-10-28 2006-05-04 Osaka University インターロイキン－６阻害剤
ES2905923T3 (es) 2005-02-08 2022-04-12 Genzyme Corp Anticuerpos de TGFbeta
KR20080082618A (ko) 2005-12-16 2008-09-11 알콘, 인코퍼레이티드 Ａｌｋ5 조절제를 사용한 안압의 조절
US20110182848A1 (en) * 2007-08-03 2011-07-28 Asterion Limited Granulocyte colony stimulating factor
TWI440469B (zh) 2008-09-26 2014-06-11 Chugai Pharmaceutical Co Ltd Improved antibody molecules
ES2715177T3 (es) * 2010-09-01 2019-06-03 Genzyme Corp Tratamiento de infarto de miocardio usando antagonistas de tgf-beta
AU2013221672B2 (en) * 2012-02-13 2017-11-09 Seattle Children's Hospital D/B/A Seattle Children's Research Institute Bispecific chimeric antigen receptors and therapeutic uses thereof
ES2713505T3 (es) 2013-03-11 2019-05-22 Genzyme Corp Anticuerpos anti-TGF-beta modificados genéticamente y fragmentos de unión a antígeno
JP6578271B2 (ja) * 2013-04-17 2019-09-18 ベイラー カレッジ オブ メディスンＢａｙｌｏｒ Ｃｏｌｌｅｇｅ Ｏｆ Ｍｅｄｉｃｉｎｅ 免疫抑制ＴＧＦ−βシグナルコンバーター
CA3008162A1 (en) 2014-12-15 2016-06-23 The Regents Of The University Of California Bispecific or-gate chimeric antigen receptor responsive to cd19 and cd20
CA2971186A1 (en) 2014-12-15 2016-06-23 The Regents Of The University Of California Cytotoxic molecules responsive to intracellular ligands for selective t cell mediated killing
RS64053B1 (sr) * 2015-10-30 2023-04-28 Univ California Polipeptidi koji reaguju na transformišući faktor rasta – beta i postupci za njihovu upotrebu
CA3018382A1 (en) 2016-03-29 2017-10-05 University Of Southern California Chimeric antigen receptors targeting cancer
CN108148863B (zh) 2016-12-05 2019-12-17 上海优卡迪生物医药科技有限公司 一种封闭il6r的用于缓解crs的car-t转基因载体及其构建方法和应用

Also Published As

Publication number Publication date
JP7104624B2 (ja) 2022-07-21
CN108884155B (zh) 2022-12-06
CN115960264A (zh) 2023-04-14
US20180312580A1 (en) 2018-11-01
US11014980B2 (en) 2021-05-25
WO2017075433A1 (en) 2017-05-04
EP3368571A1 (en) 2018-09-05
EP3368571B1 (en) 2022-12-07
KR20180092947A (ko) 2018-08-20
EP4169945A1 (en) 2023-04-26
US20210277099A1 (en) 2021-09-09
CN108884155A (zh) 2018-11-23
JP2019500012A (ja) 2019-01-10
JP2022141761A (ja) 2022-09-29
SI3368571T1 (sl) 2023-04-28
PL3368571T3 (pl) 2023-05-02
LT3368571T (lt) 2023-02-10
RS64053B1 (sr) 2023-04-28
DK3368571T3 (da) 2023-01-23
PT3368571T (pt) 2023-01-03
EP3368571A4 (en) 2019-11-06
HUE061424T2 (hu) 2023-06-28
ES2935372T3 (es) 2023-03-06
FI3368571T3 (fi) 2023-02-28

Similar Documents

Publication Publication Date Title
HRP20230239T1 (hr) Polipeptidi koji reagiraju na transformirajući faktor rasta – beta i postupci za njihovu upotrebu
JP2019500012A5 (hr)
JP7465833B2 (ja) Ｃｄ３反応性に基づくｔ細胞リクルートポリペプチド
CN107880128B (zh) 一种抗cd19的全人源抗体或抗体片段及其方法和应用
Zalfa et al. Natural killer cell interactions with myeloid derived suppressor cells in the tumor microenvironment and implications for cancer immunotherapy
ES2802994T3 (es) Anticuerpo completamente humano contra CD137 humano y uso del mismo
Goedegebuure et al. Myeloid-derived suppressor cells: general characteristics and relevance to clinical management of pancreatic cancer
EP3055330B1 (en) Molecule
CN111655716A (zh) 基于il-15的与il-7和il-21的融合体
WO2018197675A1 (en) Ror1-specific chimeric antigen receptors (car) with humanized targeting domains
WO2021030688A1 (en) Immunostimulatory multimeric binding molecules
RU2018104703A (ru) Опухолеспецифичное антитело против egfr и его применение
Han et al. Recent clinical trials utilizing chimeric antigen receptor T cells therapies against solid tumors
JP2022166297A (ja) 最適化された多機能性ｔ細胞を含むキメラ受容体ｔ細胞を使用する治療
US10927183B2 (en) Anti-human VSIG4 antibodies and uses thereof
US20210252058A1 (en) Chimeric antigen receptors with myd88 and cd40 costimulatory domains
CA3008440A1 (en) Combination therapy comprising a superagonistic antibody against interleukin-2 and a checkpoint blockade agent
US20230312671A1 (en) Grp78 targeted adoptive cell therapy
US20240216429A1 (en) Chimeric antigen receptor system with adaptable receptor specificity
US20240216427A1 (en) Chimeric antigen receptors targeting splice variants of the extracellular matrix proteins tenascin c (tnc) and procollagen 11a1 (col11a1)
KR20230160294A (ko) Upar 항체 및 이를 갖는 융합 단백질
CN113646328A (zh) 一种免疫细胞因子及其制备与用途
Mendoza-Valderrey et al. Next generation immuno-oncology strategies: unleashing NK cells activity
WO2023129995A2 (en) Chimeric antigen receptors comprising a pdz binding motif
WO2020094121A1 (en) Novel method for producing antibodies