Figure 1.

Schematic of the different CAR generations

Chimeric antigen receptors (CARs) are receptors composed of an extracellular single-chain variable fragment (scFv) comprising a variable light (VL) and variable heavy (VH) chain fused to a transmembrane domain. The intracellular signaling domain varies across generations for T cell activation. First-generation CARs contain a CD3ζ chain. Second- and third-generation CARs contain one or two co-stimulatory domains, respectively. Fourth-generation CARs, also known as TRUCKs, have an interleukin (IL) inducer, which leads to release of cytokines to improve CAR T cell function. Fifth-generation CARs are based on the second-generation CAR with an additional IL-2Rβ domain to induce JAK/STAT antigen-dependent signaling pathways for enhanced proliferation and antitumor activity.