Figure 1.
Design of the 4 generations CARs. CARs are composed of scFv, a transmembrane domain, and an intracellular signaling domain. The first-generation CARs only had an intracellular CD3ζ signaling domain (yellow). The second-generation CARs included an additional costimulatory domain, for example, CD28 (purple). The third-generation CARs added 2 costimulatory domains in the CAR design, for example, CD28 and 4-1BB (orange). The next-generation CARs introduced for example a transcription factor, for example, NFAT (green), for the production of tumor-killing cytokines upon CAR activation or added the intracellular domains of cytokine receptor for interleukin 2 (IL-2Rβ) (brown) with a binding site for the transcription factor STAT3. Created with BioRender.com. CARs = chimeric antigen receptors; NFAT = nuclear factor of activated T cells; scFvs = single-chain variable fragments.