C low+T CAR T-cells

C low+T CAR T-cells are an experimental dual-targeting chimeric antigen receptor (CAR) T-cell therapy designed for the treatment of acute myeloid leukemia (AML). This specific construct utilizes a 'dual-split' or 'AND-gate' signaling strategy to enhance therapeutic specificity and safety. The T-cell activation signals are divided between two separate CARs: a stimulatory CAR (sCAR) targeting the AML-associated antigen CLEC12a with low affinity (C low) and a costimulatory CAR (cCAR) targeting TIM3 (T) that incorporates CD28 and 4-1BB signaling domains. By requiring the presence of both antigens for full activation and employing a low-affinity binder for the stimulatory component, the therapy aims to selectively eliminate AML cells while minimizing off-tumor effects on healthy tissues. Preclinical studies presented at ASH 2023 evaluated this configuration alongside others, demonstrating its ability to induce antigen-specific responses in leukemic models.

Other names

CLEC12a low-affinity stimulatory CAR + TIM3 costimulatory CAR T-cellsdual-split CLEC12a/TIM3 CAR T-cells