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. 2018 Feb 15;9(3):282. doi: 10.1038/s41419-018-0278-6

Fig. 1. Schematic representation of the chimeric antigen receptors for adoptive cell therapy.

Fig. 1

CARs comprise an extracellular domain with a tumor-binding moiety, typically a single-chain variable fragment (scFv), followed by a hinge/spacer of varying length and flexibility, a transmembrane (TM) region, and one or more signaling domains associated with the T-cell signaling. The 1st CARs generation is equipped with the stimulatory domain of the ζ-chain; in the 2nd CARs generation the presence of costimulatory domains (CD28) provides additional signals to ensure full activation; in the 3rd generation an additional transducer domain (CD27, 41-BB or OX40) is added to the ζ-chain and CD28 to maximize strength, potency, and duration of the delivered signals; the 4th generation includes armored CARs, engineered to synthetize and deliver interleukins (green ovals)