fig1

Figure 1. Structure of the 4 generations of CAR T-cells. First-generation (1G) CARs contain an antigen recognition domain, scFv with a variable heavy and light chain connected by a linker, a transmembrane domain, and a signaling domain (CD3ζ). Second-generation (2G) CARs are similar to 1G with the addition of a costimulatory domain such as CD28 or 4-1BB. Third-generation (3G) CARs are the same as the 2G with the addition of a second costimulatory domain. Fourth-generation (4G) CARs, also known as “armored” CARs, also produce NFATs, which release a transgenic product (such as the cytokine IL-12) that can further regulate the CAR T-cell function and influence the tumor microenvironment. CAR: Chimeric antigen receptor; scFv: single-chain variable fragment; NFATs: nuclear factor of activated T-cells; IL: interleukin.