hixx + T1 CAR T-cells

hixx + T1 CAR T-cells is an experimental dual-targeting, split-signaling chimeric antigen receptor (CAR) T-cell therapy designed for the treatment of acute myeloid leukemia (AML). This 'AND-gate' approach simultaneously targets two AML-associated antigens: CLEC12a and TIM3. The system consists of two separate CAR constructs: a stimulatory CAR (sCAR) targeting CLEC12a and a costimulatory CAR (cCAR) targeting TIM3. To enhance safety and specificity, the CLEC12a sCAR (denoted as 'C hixx') is engineered with high affinity but attenuated signaling through targeted mutations in the second and third immunoreceptor tyrosine-based activation motif (ITAM) regions of the CD3ζ domain. The TIM3 cCAR (denoted as 'T1') provides essential costimulatory signals via CD28 and 41BB domains only upon binding to TIM3. This dual-split configuration is intended to minimize off-target toxicity against healthy tissues expressing only one of the antigens while maintaining potent anti-leukemic activity against cells expressing both.

Other names

CLEC12a-TIM3 dual-split CAR T-cellsCLEC-12a-TIM3 dual-split CAR T-cellsCLEC 12a-TIM3 dual-split CAR T-cellsCLEC12a(hixx) + TIM3(T1) CAR T-cells