Fig. 4. Data showing function of ON-switch CAR demonstrating antigen-specific and titratable killing of target cell population by engineered primary cytotoxic (CD8+) T cells.
Schematic illustrating the variety of control mechanisms for CAR T-cells as well as their respective mechanisms for activation or deactivation. (A) ON CARs and AND CARs replicate AND gated Boolean logic, requiring multiple signals to initiate T-cell function, thereby improving specificity. (B) Dual CARs and TanCARs replicate OR gated Boolean logic, requiring one or both signals for T-cell activation to prevent tumor escape. (C) Suicide CARs and iCARs replicate Boolean logic in which a there is NOT gate on the inhibitory signal followed by an AND gate. This means that the T-cells will only function in the condition where there is stimulatory signal with no inhibitory signal. iCARs may be used to prevent activation when encountering epitopes found on healthy tissue, while suicide CARs represent the possibility of eliminating transferred T-cells after therapy via the administration of a small molecule.