Chimeric antigen and t cell receptors and methods of use

Abstract

The invention provides a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising extracellular domain disclosed herein. Some aspects of the invention relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising the extracellular domain disclosed herein. Other aspects of the invention relate to cells comprising the CAR or the TCR and their use in a T cell therapy.

1 - 33 . (canceled) 
     
     
         34 . A method of inducing immunity against a tumor in a subject in need thereof, comprising administering to the subject an effective amount of a cell comprising a polynucleotide encoding a chimeric antigen receptor (CAR), of a vector comprising the polynucleotide, of a polypeptide encoded by the polynucleotide, or of any combination thereof, wherein the CAR comprises:
 (i) an antigen binding molecule;   (ii) a costimulatory domain, consisting of SEQ ID NO: 241; and   (iii) an intracellular activation domain from CD3 zeta;   wherein the antigen binding molecule is linked to the costimulatory domain through 1 to 6 heterologous amino acids; and   wherein the antigen is selected from ErbB2 (HER2/neu), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), CD19, CD20, CD30, CD40, disialoganglioside GD2, ductal-epithelial mucine, gp36, TAG-72, glycosphingolipids, glioma-associated antigen, B-human chorionic gonadotropin, alphafetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RU1, RU2 (AS), intestinal carboxyl esterase, mut hsp70-2, M-CSF, prostase, prostase specific antigen (PSA), PAP, NY-ESO-1, LAGA-1a, p53, mutated p53, prostein, PSMA, survivin and telomerase, prostate-carcinoma tumor antigen-1 (PCTA-1), MAGE, MAGE-A1, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin growth factor (IGFI)-I, IGF-II, IGFI receptor, a major histocompatibility complex (MHC) molecule presenting a tumor-specific peptide epitope, 5T4, ROR1, Nkp30, NKG2D, tumor stromal antigen, the extra domain A (EDA) of fibronectin, the extra domain B (EDB) of fibronectin, the AI domain of tenascin-C (TnC AI,) fibroblast associated protein (fap), CD3, CD4, CD8, CD24, CD25, CD33, CD34, CD133, CD138, CTLA-4, B7-1 (CD80), B7-2 (CD86), endoglin, a major histocompatibility complex (MHC) molecule, an HIV-specific antigen HIV gp120, an EBV-specific antigen, a CMV-specific antigen, an HPV-specific antigen, an HBV-specific antigen, an HCV-specific antigen, a Lassa Virus-specific antigen, an Influenza Virus-specific antigen, CD38, CA-125, MUC-1, CD44, surface adhesion molecule, vascular endothelial growth factor receptor-2 (VEGFR2), high molecular weight-melanoma associated antigen (HMW-MAA), epithelial tumor antigen, IL-13R-a2, GD2, GD3, prostate-specific antigen, melanoma-associated antigen, mutated ras, folate binding protein, HIV-1 envelope glycoprotein gp41, CD123, CD23, CD56, c-Met, HERV-K, IL-11Ralpha, kappa chain, lambda chain, CSPG4, HER1-HER2 in combination, and HER2-HER3 in combination.   
     
     
         35 . A method of treating cancer in a subject in need thereof, comprising administering to the subject an effective amount of a cell comprising a polynucleotide encoding a chimeric antigen receptor (CAR), of a vector comprising the polynucleotide, of a polypeptide encoded by the polynucleotide, of a composition comprising the polynucleotide, or of any combination thereof, wherein the CAR comprises:
 (i) an antigen binding molecule;   (ii) a costimulatory domain, consisting of SEQ ID NO: 241; and   (iii) an intracellular activation domain from CD3 zeta;   wherein the antigen binding molecule is linked to the costimulatory domain through 1 to 6 heterologous amino acids; and   wherein the antigen is selected from ErbB2 (HER2/neu), carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), epidermal growth factor receptor (EGFR), EGFR variant III (EGFRvIII), CD19, CD20, CD30, CD40, disialoganglioside GD2, ductal-epithelial mucine, gp36, TAG-72, glycosphingolipids, glioma-associated antigen, B-human chorionic gonadotropin, alphafetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RU1, RU2 (AS), intestinal carboxyl esterase, mut hsp70-2, M-CSF, prostase, prostase specific antigen (PSA), PAP, NY-ESO-1, LAGA-1a, p53, mutated p53, prostein, PSMA, survivin and telomerase, prostate-carcinoma tumor antigen-1 (PCTA-1), MAGE, MAGE-A1, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin growth factor (IGFI)-I, IGF-II, IGFI receptor, a major histocompatibility complex (MHC) molecule presenting a tumor-specific peptide epitope, 5T4, ROR1, Nkp30, NKG2D, tumor stromal antigen, the extra domain A (EDA) of fibronectin, the extra domain B (EDB) of fibronectin, the AI domain of tenascin-C (TnC AI,) fibroblast associated protein (fap), CD3, CD4, CD8, CD24, CD25, CD33, CD34, CD133, CD138, CTLA-4, B7-1 (CD80), B7-2 (CD86), endoglin, a major histocompatibility complex (MHC) molecule, an HIV-specific antigen HIV gp120, an EBV-specific antigen, a CMV-specific antigen, an HPV-specific antigen, an HBV-specific antigen, an HCV-specific antigen, a Lassa Virus-specific antigen, an Influenza Virus-specific antigen, CD38, CA-125, MUC-1, CD44, surface adhesion molecule, vascular endothelial growth factor receptor-2 (VEGFR2), high molecular weight-melanoma associated antigen (HMW-MAA), epithelial tumor antigen, IL-13R-a2, GD2, GD3, prostate-specific antigen, melanoma-associated antigen, mutated ras, folate binding protein, HIV-1 envelope glycoprotein gp41, CD123, CD23, CD56, c-Met, HERV-K, IL-11Ralpha, kappa chain, lambda chain, CSPG4, HER1-HER2 in combination, and HER2-HER3 in combination.   
     
     
         36 . The method of  claim 34 , wherein the cancer is a hematologic cancer. 
     
     
         37 . The method of  claim 34 , wherein the cancer is of the white blood cells. 
     
     
         38 . The method of  claim 34 , wherein the cancer is of the plasma cells. 
     
     
         39 . The method of  claim 34 , wherein the cancer is leukemia, lymphoma, or myeloma. 
     
     
         40 . The method of  claim 34 , wherein the cancer is acute lymphoblastic leukemia (ALL) (including non T cell ALL), acute myeloid leukemia, B cell prolymphocytic leukemia, B-cell acute lymphoid leukemia (“BALL”), blastic plasmacytoid dendritic cell neoplasm, Burkitt's lymphoma, chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), chronic myeloid leukemia, chronic or acute leukemia, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), hairy cell leukemia, Hodgkin's Disease, malignant lymphoproliferative conditions, MALT lymphoma, mantle cell lymphoma, Marginal zone lymphoma, monoclonal gammapathy of undetermined significance (MGUS), multiple myeloma, myelodysplasia and myelodysplastic syndrome, non-Hodgkin's lymphoma (NHL), plasma cell proliferative disorder (including asymptomatic myeloma (smoldering multiple myeloma or indolent myeloma), plasmablastic lymphoma, plasmacytoid dendritic cell neoplasm, plasmacytomas (including plasma cell dyscrasia; solitary myeloma; solitary plasmacytoma; extramedullary plasmacytoma; and multiple plasmacytoma), POEMS syndrome (also known as Crow-Fukase syndrome; Takatsuki disease; and PEP syndrome), primary mediastinal large B cell lymphoma (PMBC), small cell- or a large cell-follicular lymphoma, splenic marginal zone lymphoma (SMZL), systemic amyloid light chain amyloidosis, T-cell acute lymphoid leukemia (“TALL”), T-cell lymphoma, transformed follicular lymphoma, or Waldenstrom macroglobulinemia, or a combination thereof. 
     
     
         41 . The method of  claim 34 , wherein the antigen binding molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises 3 complementarity determining regions (CDRs) and the VL comprises 3 CDRs. 
     
     
         42 . The method of  claim 34 , wherein the antigen binding molecule specifically binds an antigen selected from the group consisting of 5T4, alphafetoprotein, CA-125, carcinoembryonic antigen, CD19, CD20, CD22, CD23, CD30, CD33, CD56, CD123, CD138, c-Met, CSPG4, EGFRvIII, epithelial tumor antigen, folate binding protein, GD2, GD3, HER1-HER2 in combination, HER2-HER3 in combination, ErbB2 (HER2/neu), HERV-K, HIV-1 envelope glycoprotein gp41, HIV-1 envelope glycoprotein gp120, IL-IIRalpha, kappa chain, lambda chain, melanoma-associated antigen, mesothelin, MUC-1, mutated p53, mutated ras, prostate-specific antigen, ROR1, or VEGFR2. 
     
     
         43 . The method of  claim 34 , wherein the antigen binding molecule comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises 3 complementarity determining regions (CDRs) and the VL comprises 3 CDRs. 
     
     
         44 . The method of  claim 34 , wherein the antigen binding molecule specifically binds an antigen selected from the group consisting of 5T4, alphafetoprotein, CA-125, carcinoembryonic antigen, CD19, CD20, CD22, CD23, CD30, CD33, CD56, CD123, CD138, c-Met, CSPG4, EGFRvIII, epithelial tumor antigen, folate binding protein, GD2, GD3, HER1-HER2 in combination, HER2-HER3 in combination, ErbB2 (HER2/neu), HERV-K, HIV-1 envelope glycoprotein gp41, HIV-1 envelope glycoprotein gp120, IL-IIRalpha, kappa chain, lambda chain, melanoma-associated antigen, mesothelin, MUC-1, mutated p53, mutated ras, prostate-specific antigen, ROR1, or VEGFR2. 
     
     
         45 . The method of  claim 34 , wherein the activation domain comprises SEQ ID NO: 9 or SEQ ID NO: 251. 
     
     
         46 . The method of  claim 34 , wherein the activation domain is encoded by a nucleotide sequence comprising SEQ ID NO: 8. 
     
     
         47 . The method of  claim 34 , wherein the CAR further comprises a leader peptide. 
     
     
         48 . The method of  claim 47 , wherein the leader peptide comprises an amino acid sequence comprising SEQ ID NO: 11. 
     
     
         49 . The method of  claim 47 , wherein the leader peptide is encoded by a nucleotide sequence comprising SEQ ID NO: 10. 
     
     
         50 . The method of  claim 34 , comprising administering an effective amount of a vector comprising the polynucleotide. 
     
     
         51 . The method of  claim 50 , wherein the vector is an adenoviral vector, an adenovirus-associated vector, a DNA vector, a lentiviral vector, a plasmid, a retroviral vector, or an RNA vector, or any combination thereof. 
     
     
         52 . The method of  claim 34 , comprising administering an effective amount of a polypeptide encoded by the polynucleotide. 
     
     
         53 . The method of  claim 34 , comprising administering an effective amount of a cell comprising the polynucleotide. 
     
     
         54 . The method of  claim 53 , wherein the cell is a T cell. 
     
     
         55 . The method of  claim 54 , wherein the T cell is an allogeneic T cell, an autologous T cell, an engineered autologous T cell, or a tumor-infiltrating lymphocyte (TIL). 
     
     
         56 . The method of  claim 54 , wherein the T cell is a CD4+ T cell. 
     
     
         57 . The method of  claim 54 , wherein the T cell is a CD8+ T cell. 
     
     
         58 . The method of  claim 54 , wherein the T cell is an in vitro cell. 
     
     
         59 . The method of  claim 54 , wherein the T cell is an autologous T cell. 
     
     
         60 . The method of  claim 34 , comprising administering an effective amount of a composition comprising the polynucleotide. 
     
     
         61 . The method of  claim 34 , wherein the encoded CAR further comprises an intracellular domain comprising a signaling region of 4-1BB/CD137.