Figure 1.

The differences in tumor antigen recognition between conventional TCRs and synthetic CARs. (A) TCR recognition of tumor antigens is restricted by MHC complex molecules, and the suboptimal efficiency of cancer cell killing by conventional T cells may be due in part to the lack of CD80/86 expression on tumor cells. The CD8 coreceptor has been omitted from the illustration for purpose of simplicity. (B) Synthetic CARs recognize tumor-associated antigens on the surface of cancer cells through the single-chain variable fragment (scFv) domain. These interactions then simultaneously activate both the CD3-mediated primary signal and the CD28/4-1BB-mediated secondary signal in T cells. (C) The scFv domain is derived from a monoclonal antibody and consists of the variable regions from the heavy chain (V_H) and light chain (V_L) linked by a flexible linker sequence.