Fig. 3

Five generations of CAR-T cells. The first-generation CAR-T cells only contain one intracellular signal domain CD3ζ. The second-generation CARs consist of a co-stimulatory domain, including 4-1BB (CD137) or CD28, whereas the third-generation ones have two co-stimulatory domains. The fourth-generation CAR-T cells, based on the second-generation CARs, can induce cytokine production. The fifth-generation CAR-T cells are also based on the second-generation CARs, containing intracellular domains of cytokine receptors, such as IL-2Rβ chain fragment