Fig. 1.

The basic structure of CAR-T cell generations. The first generation of CARs contains only a CD3ζ as a well-documented intracellular signal domain. The second and third generations of CARs involve one or two costimulatory molecules in addition to CD3ζ, respectively. As well, the fourth generation of CAR-T cells strongly motivates the downstream transcription factor to prompt cytokine generation following interrelation between CAR and target antigen. Prominently, the genome edition technologies, such as CRISPR-Cas9, have been widely used to construct TRAC (TCR)-deficient CAR-T cells, establishing fifth generation of CAR-T cells