Fig. 2

“AND” and “NOT” logic-gated CAR-T cells for alleviating on-target, off-tumor toxicities. a Dual CAR-T cells: “AND” logic gate. Two distinct CARs are coexpressed with complementary signaling domains in one T cell that fully activates the T cell only in the presence of both cognate antigens. b Synthetic Notch Receptor System: “AND” logic gate. In the presence of cognate antigen of CAR1, SynNotch receptor induces the conditional expression of CAR2 in a transcriptional manner, thereby targeting to the second antigen, and finally achieving highly specific activation of T cell. c Trivalent CAR T cells: “AND” logic gate. Trivalent CAR-T cell response to tumor-specific expression patterns to overcome the immunosuppression of TME, rather than adding additional CARs targeting TAAs. d Dual CAR-T cells: “NOT” logic gate. iCAR-T cells selectively kill target cells only expressing one antigen, whereas off-target cells co-expressing another inhibitory ligand recognized by iCAR were protected from attack, allowing T cells to distinguish target cells from the off-target cells