Fig. 1

Generations of CARs. CARs are constructed from a single-chain variable fragment (scFv) coupled with a CD3ζ molecule and a co-stimulatory molecule such as CD28. The scFv consists of a variable light chain domain (VL) and a variable heavy chain domain (VH). CD3ζ initiates and triggers antigen-specific immune responses. The CD28 domain promotes faster expansion of CAR-T cells. The 41BB domain is typically used to enhance in vivo persistence of the cells. IL-12 increases the survival of CAR-T cells in the immunosuppressive tumor microenvironment. The IL-2Rβ chain domain overcomes tumor-inhibitory microenvironments, enhancing the anti-tumor effects of T cells