Chimeric antigen receptor and methods of use thereof

A method of stimulating a T-cell mediated immune response to a cancer cell in a human, the method comprising:

• A) administering to the human an effective amount of T lymphocytes, wherein the T lymphocytes are genetically modified to produce a heterodimeric chimeric antigen receptor (CAR) comprising a first polypeptide and a second polypeptide, wherein the first and second polypeptides are two separate polypeptides, wherein:
• a) the first polypeptide comprises:
• i) an extracellular antigen binding domain specific for an epitope on the cancer cell in the human;
• ii) a transmembrane domain;
• and
• iii) a first member of a dimerization pair;
• and
• b) the second polypeptide comprises:
• i) a transmembrane domain;
• ii) a second member of the dimerization pair;
• and
• iii) an intracellular signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM), wherein the intracellular signaling domain provides signal transduction activity,
• wherein the first polypeptide, the second polypeptide or both the first and second polypeptides comprise an intracellular costimulatory polypeptide, and
• B) administering to the human an effective amount of a dimerizing agent, wherein the dimerizing agent induces dimerization of the heterodimeric CAR when expressed in the cell membranes of the T lymphocytes, wherein said dimerization provides for stimulation of the T-cell mediated immune response in the presence of the epitope on the cancer cell to which said extracellular antigen binding domain specifically binds.