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Chimeric antigen receptors (CARs). The first-generation CARs only have CD3 zeta signaling domain; the second-generation CARs include one CD28 or 4-1BB co-stimulatory components combined with CD3 zeta signaling domain; the third-generation CARs include two co-stimulatory domains; the fourth-generation CARs are designed with new elements including a controllable suicide gene like caspase 9 or loaded with IL-12 secretion. Reproduced with permission from: Barth et al. (39).
