Figure 1. Structure and evolution of CARs.

CARs are composed of an antigen-recognition domain (mainly scFv of monoclonal antibodies) fused to a hinge/transmembrane domain and intracellular signaling domains able to transduce activation signals to CAR T cells. Modification in the intracellular domains gave rise to a different generation of CAR T cells from the first generation, which included a CD3ζ motif, to the second and third generations, which included one or two costimulatory domains, respectively. V_H, variable heavy chain; V_L, variable light chain.