Figure 3.

The logic gatings in modular CAR. (A) OR logic: the modular CAR-T cell can eliminate different cancer cells with various switching modules, which are recognized by the same CAR-T cell but target different antigens on cancer cells. (B) AND logic: the antigen-binding domain and costimulator are separated into two CARs targeting different antigens and cotransduced into T cells. Only when tumor cells express two antigens simultaneously can they be recognized and attacked by these CAR-T cells. (C) NOT logic: a tumor-associated antigen is expressed on cancer cells and normal cells simultaneously, while another antigen is expressed on normal cells only. The two modules binding to them are complementary in the site recognized by the signaling module. The extra target works as a safety label to prevent the “on-target, off-tumor” toxicity of CAR-T cells.