Figure 2.

CAR structure. CARs are comprised of an antigen-recognition ectodomain derived from the single-chain variable fragment (scFv) of a monoclonal antibody connected by a flexible hinge and transmembrane segment to an intracellular endodomain. Originally derived from the CD3ζ domain of the classical TCR in (A) first generation CARs, this intracellular signaling component may contain (B) one (second generation) or (C) two (third generation) additional costimulatory domains that enhance the proliferation, persistence, and efficacy of adoptively transferred cells.