CAM-M

CAM-M is an affinity-tuned chimeric antigen receptor (CAR) targeting the interleukin-3 receptor alpha (CD123), developed for the treatment of acute myeloid leukemia (AML). It is a "medium-affinity" mutant derived from a wild-type anti-CD123 CAR (clone 7G3) through single-residue substitution in the single-chain fragment variable (scFv) region. This mutation results in a 10-fold lower binding affinity compared to the wild-type CAR, primarily driven by a slower association rate (Kon). This tuning is intended to improve the therapeutic index by reducing "on-target, off-tumor" toxicity against healthy tissues with low CD123 expression (such as endothelium and monocytes) while maintaining potent cytotoxic activity against high-density CD123+ leukemic blasts. The CAR construct is a third-generation design incorporating CD28 and OX40 co-stimulatory domains and the CD3-zeta signaling chain. In research settings, it is expressed in cytokine-induced killer (CIK) cells using the Sleeping Beauty transposon system.

Other names

anti-CD123 CAR affinity mutant Manti-CD-123 CAR affinity mutant Manti-CD 123 CAR affinity mutant Manti-CD123-CD28-OX40-CD3z CAR-CIK (CAM-M)