Chimeric Antigen Receptors. Chimeric antigen receptor (CAR) molecules link an extracellular single-chain variable fragment (scFv) to the CD3? intracellular domain of the T cell receptor. First-generation constructs were followed by combination with one (second generation) or two (third generation) additional costimulatory domains. From Maus MV, et al. Blood 2014; 123:2625-2635.