Fig. 1.

Schematic structure of CAR generations. First-generation CARs include an extracellular domain consisting of the scFv, a transmembrane domain; and an intracellular signaling module (endodomain). Additional one or two costimulatory endodomains such as CD28, CD137 (4-1BB), and CD134 (OX40) promote T cell activation and proliferation in second and third CAR generations respectively. CAR, Chimeric antigen receptor; NFAT; nuclear factor of activated T cells transcription factor; scFv, single-chain variable fragment; TAA, tumor-associated antigens.