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US 12,721,892 B2Granted
Methods and compositions for chimeric antigen receptor targeting cancer cells
AssigneeThe University of North Carolina at Chapel Hill
InventorsGianpietro Dotti, Chuang Sun, Peishun Shou, Yang Xu
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Abstract
The present invention provides chimeric antigen receptors (CAR) and methods of use in the treatment of diseases and disorders.
Claims12
A method of reducing a T cell-mediated immune stimulation to a target cell population or tissue in a subject, comprising:
- a) administering to the subject an effective amount of a T cell comprising a vector, wherein the vector comprises a first nucleic acid molecule encoding a chimeric antigen receptor (CAR) and a second nucleic acid molecule encoding a polypeptide comprising an FKBP linked to SHP1,
- wherein the CAR comprises a hinge region, a transmembrane domain, a CD3ζ domain, an scFv, a CD28 costimulatory molecule, and an FKBP-rapamycin binding domain (FRB), wherein the scFv binds to TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, GD2, GD3, BCMA, Tn Ag, PSMA, ROR1, FLT3, FAP, TAG72, CD38, CD44v6, CEA, EPCAM, B7H3, KIT, IL-13Ra2, Mesothelin, IL-11Ra, PSCA, PRSS21, VEGFR2, LewisY, CD24, PDGFR-β, SSEA-4, CD20, FRα, ERBB2(Her2/neu), MUC1, EGFR, NCAM, Prostase, PAP, ELF2M, EphB2, IGF-I receptor, CAIX, LMP2, gp100, bcr-abl, tyrosinase, EphA2, GM1, sLe, GM3, TGSS, HMWMAA, FRβ, TEM1/CD248, TEM7R, CLDN6, GPRCSD, CXORF61, CD97, CD179a, ALK, PSA, PLAC1, GloboH, NY-BR-1, UPK2, HAVCR1, ADRB3, PANX3, GPR20, LY6K, OR51E2, TARP, WT1, NY-ESO-1, LAGE-1a, MAGE-AL legumain, HPV E6, E7, MAGE A1, ETV6-AML, Sp17, XAGE1, Tie 2, MAD-CT-1, MAD-CT-2, FRA1, p53, p53 mutants, prostein, survivin, PCTA-1/Galectin8, MelanA/MART1, Ras, hTERT, ML-IAP, ER, TMPRSS2 ETS fusion gene, NA17, PAX3, AR, cyclin B1, MYCN, RhoC, TRP-2, CYP1B1, BORIS, SART3, PAX5, OY-TES1, LCK, AKAP-4, SSX2, RAGE-1, RU1, RU2, CEA, hsp70-2, CD79a, CD79b, CD72, LAIR1, FCAR, LILRA2, CD300LF, CLEC12A, BST2, EMR2, LY75, GPC3, CLN18.2, CLN6, FCRL5, IGLL1, or any variant thereof;
- and
- b) administering an effective amount of AP21967 and/or functional analogue thereof, wherein the AP21967 and/or functional analogue thereof dimerizes the CAR and the polypeptide,
- thereby reducing the T cell-mediated immune stimulation.
2 more elements
A method of reducing CAR T cell-mediated immune stimulation bystander cytotoxicity in a subject having cancer, comprising:
- a) administering to the subject an effective amount of a T cell comprising a vector,
- wherein the vector comprises a first nucleic acid molecule encoding a chimeric antigen receptor (CAR) and a second nucleic acid molecule encoding a polypeptide comprising an FKBP linked to SHP1,
- wherein the CAR comprises a hinge region, a transmembrane domain, a CD3ζ domain, an scFv, a CD28 costimulatory molecule, and an FKBP-rapamycin binding domain (FRB), wherein the scFv binds to TSHR, CD19, CD123, CD22, CD30, CD171, CS-1, CLL-1, CD33, EGFRvIII, GD2, GD3, BCMA, Tn Ag, PSMA, ROR1, FLT3, FAP, TAG72, CD38, CD44v6, CEA, EPCAM, B7H3, KIT, IL-13Ra2, Mesothelin, IL-11Ra, PSCA, PRSS21, VEGFR2, LewisY, CD24, PDGFR-β, SSEA-4, CD20, FRα, ERBB2(Her2/neu), MUC1, EGFR, NCAM, Prostase, PAP, ELF2M, EphB2, IGF-I receptor, CAIX, LMP2, gp100, bcr-abl, tyrosinase, EphA2, GM1, sLe, GM3, TGS5, HMWMAA, FRβ, TEM1/CD248, TEM7R, CLDN6, GPRC5D, CXORF61, CD97, CD179a, ALK, PSA, PLAC1, GloboH, NY-BR-1, UPK2, HAVCR1, ADRB3, PANX3, GPR20, LY6K, OR51E2, TARP, WT1, NY-ESO-1, LAGE-1a, MAGE-A1, legumain, HPV E6,E7, MAGE A1, ETV6-AML, Sp17, XAGE1, Tie 2, MAD-CT-1, MAD-CT-2, FRA1, p53, p53 mutants, prostein, survivin, PCTA-1/Galectin8, MelanA/MART1, Ras, hTERT, ML-IAP, ER, TMPRSS2 ETS fusion gene, NA17, PAX3, AR, cyclin B1, MYCN, RhoC, TRP-2, CYP1B1, BORIS, SART3, PAX5, OY-TES1, LCK, AKAP-4, SSX2, RAGE-1, RU1, RU2, CEA, hsp70-2, CD79a, CD79b, CD72, LAIR1, FCAR, LILRA2, CD300LF, CLEC12A, BST2, EMR2, LY75, GPC3, CLN18.2, CLN6, FCRL5, IGLL1, or any variant thereof;
- and
- b) administering an effective amount of AP21967 and/or functional analogue thereof, wherein the AP21967 and/or functional analogue thereof dimerizes the CAR and the polypeptide,
- thereby reducing the CAR T cell-mediated immune stimulation and bystander cytotoxicity.
3 more elements
A method of treating a CD19-expressing cancer in a subject in need thereof, comprising:
- a) administering to the subject an effective amount of a T cell comprising a vector,
- wherein the vector comprises a first nucleic acid molecule encoding a chimeric antigen receptor (CAR) and a second nucleic acid molecule encoding a polypeptide comprising an FKBP linked to SHP1,
- wherein the CAR comprises a hinge region, a transmembrane domain, a CD35 domain, an scFv, a CD28 costimulatory molecule, and an FKBP-rapamycin binding domain (FRB), wherein the scFv binds to CD19 or any variant thereof;
- and
- b) administering an effective amount of AP21967 and/or functional analogue thereof, wherein the AP21967 and/or functional analogue thereof dimerizes the CAR and the polypeptide,
- thereby treating the subject having a CD19-expressing cancer.
3 more elements
Dependencies are inferred from the claim text.