inhibitory chimeric antigen receptor T-cell

Inhibitory chimeric antigen receptor T-cells (iCARs) represent a cell therapy platform designed to improve the safety profile of CAR-T treatments by reducing off-tumor, on-target toxicity. The technology utilizes a dual-receptor system: an activating CAR that targets a tumor-associated antigen and an inhibitory CAR (iCAR) that recognizes an antigen expressed on healthy tissues. The iCAR is engineered with the intracellular signaling domains of immune checkpoint molecules, such as PD-1 or CTLA-4. When the T-cell encounters a normal cell expressing the inhibitory ligand, the iCAR provides a dominant negative signal that dampens or shuts down the T-cell activation triggered by the activating CAR. This "AND-NOT" logic gate allows for more precise targeting of cancer cells while sparing healthy tissues. Sing Pharma (formerly Singularity Therapeutics) developed an iCAR platform utilizing PD-1 and CTLA-4 signaling for oncology indications, which remained in the preclinical stage.

Other names

Inhibitory CAR-TiCAR-T