SynNotch CD123 + CLL1 CAR-T

SynNotch CD123 + CLL1 CAR-T is an investigational cell therapy that utilizes a synthetic Notch (SynNotch) circuit to provide "AND-gate" logic for the treatment of acute myeloid leukemia (AML). The T-cells are engineered with a SynNotch receptor containing an anti-CD123 single-chain variable fragment (scFv); upon binding to CD123 on tumor cells, the receptor releases a Gal4VP64 transcription factor that induces the expression of a second receptor, a chimeric antigen receptor (CAR) specific for C-type lectin-like molecule-1 (CLL1). This sequential activation ensures that the CAR is only expressed in the presence of CD123, thereby protecting healthy neutrophils (which express CLL1 but not CD123) from off-target destruction. This approach aims to reduce the risk of severe treatment-induced granulocytopenia while maintaining potent anti-leukemic activity and improving T-cell persistence through reduced exhaustion and enhanced memory differentiation.

Other names

SynNotch CD123-CLL1 CAR-TSynNotch CD123 and CLL1 CAR-T