CD79A CHIMERIC ANTIGEN RECEPTORS
The invention provides improved compositions for adoptive cell therapies for cancers that express CD79A.
1 .- 69 . (canceled)
70 . A chimeric antigen receptor (CAR) comprising:
a) an extracellular domain that comprises an anti-CD79A antibody, or antigen binding fragment thereof, that binds a human CD79A polypeptide; wherein the anti-CD79A antibody, or antigen binding fragment thereof, comprises a variable light chain sequence comprising complementarity-determining region (CDR) sequences CDRL1-CDRL3 set forth in SEQ ID NOs: 1-3, and a variable heavy chain sequence comprising CDRH1-CDRH3 sequences set forth in SEQ ID NOs: 4-6; and wherein the variable heavy chain is positioned c-terminal to the variable light chain;
b) a CD8α hinge region;
c) a CD8α transmembrane domain;
d) a 4-1BB (CD137) intracellular co-stimulatory signaling domain; and
e) a CD3ζ primary signaling domain.
71 . The CAR of claim 70 , wherein the anti-CD79A antibody, or antigen binding fragment thereof, that binds the human CD79A polypeptide is selected from the group consisting of: a Fab′ fragment, a F(ab′)2 fragment, a bispecific Fab dimer (Fab2), a trispecific Fab trimer (Fab3), an Fv, an single chain Fv protein (“scFv”), a bis-scFv, (scFv)2, a minibody, a diabody, a triabody, a tetrabody, and a disulfide stabilized Fv protein (“dsFv”).
72 . The CAR of claim 71 , wherein the anti-CD79A antibody, or antigen binding fragment thereof, that binds the human CD79A polypeptide is an scFv.
73 . The CAR of claim 70 , wherein the anti-CD79A antibody, or antigen binding fragment thereof, comprises a variable light chain sequence as set forth in SEQ ID NO: 7 and/or a variable heavy chain sequence as set forth in SEQ ID NO: 8.
74 . The CAR of claim 70 , comprising an amino acid sequence as set forth in SEQ ID NO: 26.
75 . A polypeptide comprising the CAR of claim 70 , wherein the polypeptide further comprises a signal peptide.
76 . A polynucleotide encoding a CAR of claim 70 or comprising a sequence as set forth in SEQ ID NO: 32.
77 . A vector comprising the polynucleotide of claim 76 .
78 . The vector of claim 77 , wherein the vector is an expression vector.
79 . The vector of claim 77 , wherein the vector is a viral vector.
80 . The vector of claim 77 , wherein the vector is a retroviral vector.
81 . The vector of claim 77 , wherein the vector is a lentiviral vector.
82 . An immune effector cell comprising the vector of claim 77 .
83 . A composition comprising the immune effector cell of claim 82 and a physiologically acceptable excipient.
84 . A method of treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the composition of claim 83 .
85 . The method of claim 84 , wherein the cancer is a hematological malignancy.
86 . The method of claim 85 , wherein the cancer is non-Hodgkin's lymphoma, acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), multiple myeloma (MM), acute myeloid leukemia (AML), or chronic myeloid leukemia (CML).
87 . The method of claim 86 , wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma, small lymphocytic lymphoma (SLL), diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL).
88 . The method of claim 87 , wherein the non-Hodgkin's lymphoma is diffuse large B cell lymphoma (DLBCL).
89 . The method of claim 87 , wherein the non-Hodgkin's lymphoma is Burkitt's lymphoma.