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CAM-H1 is a high-affinity chimeric antigen receptor (CAR) mutant designed to target the interleukin-3 receptor alpha (IL-3RA; CD123), which is overexpressed in acute myeloid leukemia (AML) and leukemia stem cells. It was developed as part of a research effort to optimize CAR-T cell therapy by tuning binding affinity to improve the therapeutic index. CAM-H1 was created by introducing a single amino acid substitution into the antigen-binding loops of a wild-type (WT) anti-CD123 single-chain fragment variable (scFv) derived from the 7G3 monoclonal antibody clone. This CAR is typically expressed in cytokine-induced killer (CIK) cells—a heterogeneous population of T cells with natural killer-like properties—using the non-viral Sleeping Beauty transposon system. In preclinical studies, CAM-H1-CIK cells demonstrated potent cytotoxic activity and cytokine production (such as IFN-γ and IL-2) against CD123-positive AML cells, serving as a high-affinity reference for comparing the efficacy and safety of lower-affinity mutants aimed at reducing on-target, off-tumor toxicity.
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