Figure 1.

Schematic representation of first, second, third, or fourth generations of chimeric antigen receptors (CAR). CARs are hybrid receptors that comprise an antibody-derived extracellular binding domain selected against a molecular target, usually in the form of a single-chain variable fragment (scFv), and a hinge/transmembrane domain fused to an intracellular signaling domain responsible for activating T cells. First-generation CARs have only one CD3ζ chain in the intracellular domain for activating T cells. Second- and third-generation CARs harbor one and two additional intracellular co-stimulatory domains, respectively. Fourth-generation CARs are CARs of second- or third-generation designed to induce expression of transgenic products constitutively or by induction, such as cytokines or monoclonal antibodies.