CAR structure, according to signaling domains. CAR molecules link an extracellular single-chain variable fragment (scFv) to intracellular signaling domains. The intracellular component includes the CD3ζ intracellular signaling domain of the T-cell receptor either alone (first generation) or in combination with 1 (second generation) or 2 (third generation) costimulatory domains. Reprinted with permission from Maus et al.¹⁹