Figure 1.

A detailed anatomy of different CAR generations. First-generation CARs contain only a primary stimulation domain (e.g. CD3ζ). Second-generation CARs harbor one costimulatory domain (CsD) whereas third-generation CARs have two CsDs (a primary CsD and a secondary CsD). Fourth-generation CARs, also known as T cell redirected for universal cytokine-mediated killing (TRUCKs) or armored CARs, are based on second-generation CARs and are paired with a cytokine secretion inducer (e.g. IL-12). Fifth-generation CARs are also tailored versions of second-generation CARs as they contain an intracellular domain of a cytokine receptor (e.g. IL-2Rβ). SD, stimulation domain.