Chimeric antigen receptor and methods of use thereof

One or more nucleic acids comprising a nucleotide sequence(s) encoding a heterodimeric chimeric antigen receptor (CAR) comprising:

• a first polypeptide comprising a first member of a dimerization pair, a first transmembrane domain, and an intracellular signaling domain;
• and
• a second polypeptide comprising a scFv or VHH domain that specifically binds to mesothelin, a second member of the dimerization pair, and a second transmembrane domain;
• wherein:
• the first and second members of the dimerization pair are intracellular,
• a dimerizing agent dimerizes the heterodimeric CAR when the first and second polypeptides are expressed by a cell with the dimerizing agent bound between the dimerization pair members of the first and second polypeptides,
• the first polypeptide does not comprise an antigen-binding domain and the second polypeptide does not comprise an intracellular signaling domain capable of inducing cell activation, and
• activation of the cell by the formed heterodimeric CAR binding mesothelin or said antigen is increased as compared to activation of the cell in the absence of the dimerizing agent.