CAM-L

CAM-L is an experimental, low-affinity chimeric antigen receptor (CAR) mutant designed to target the interleukin-3 receptor alpha (CD123/IL-3RA). It was developed to improve the safety profile of CAR-based therapies for acute myeloid leukemia (AML) by reducing "on-target, off-tumor" toxicity against healthy tissues with low CD123 expression, such as endothelial cells and monocytes. CAM-L features a single-residue substitution in the single-chain fragment variable (scFv) domain, resulting in a 100-fold lower binding affinity compared to the wild-type anti-CD123 CAR. This reduction in affinity is achieved through a slower association rate (Kon), which raises the activation threshold for T-cell signaling, favoring the recognition of high-antigen-density leukemia cells over low-antigen-density healthy cells. In preclinical studies, CAM-L was expressed in cytokine-induced killer (CIK) cells using the Sleeping Beauty transposon system.

Other names

anti-CD123 CAM-Lanti-CD-123 CAM-Lanti-CD 123 CAM-Llow-affinity anti-CD123 CAR