Fig. 2.

CAR T cell engineering. The specificity of T cells against tumor cells is mediated by CAR proteins. CAR is a combination of extracellular proteins and is usually derived from antibodies and intracellular signaling modules derived from T cell signaling proteins. First-generation CARs have been composed of CD3ζ, while adding  a costimulatory endodomain including CD28 or 4BB to CD3ζ has led to the creation of second-generation CARs. Third-generation cars include two costimulatory domains fused to CD3ζ. VH, variable heavy chain; VL, variable light chain; scFv, single-chain variable fragment. Generation of CAR T cells leads to the initiation of different signaling pathways which caused cell survival, proliferation, and cytokine production