Fig. 2.

Structure of CARs. All chimeric antigen receptors (CARs) have the same extracellular structure consisting of single-chain variable fragment (ScFV) part of an antibody which is specific for a target tumour antigen. First-generation CARs contain only one intracellular signalling component: CD3ζ. Addition of a co-stimulatory domain, such as CD28 or 4-1BB, to the CD3ζ created second-generation CARs. Third-generation CARs contain two co-stimulatory domains in addition to CD3ζ. Fourth-generation CARs can activate downstream transcription factors, such as NFAT, following CAR antigen recognition resulting in cytokine production