CD38, CLL-1 (CLEC12A)

Class

Chimeric antigen receptor (CAR) T-cell therapy (dual-antigen-targeted)

CD38 and CLL-1 (also called CLEC12A) are two proteins found on the surface of certain blood cells, including malignant cells in acute myeloid leukemia (AML). CD38 is an enzyme-receptor expressed broadly on plasma cells, activated lymphocytes, and many leukemic blasts, while CLL-1 is a lectin-type receptor found predominantly on myeloid leukemia cells and their progenitor "stem-like" populations, with much lower expression on healthy tissue. A chimeric antigen receptor (CAR) T-cell therapy re-engineers a patient's own T lymphocytes to express a synthetic receptor that recognizes a chosen surface antigen, triggering the T cell to kill any cell displaying it. Targeting a single antigen such as CD38 alone can lead to toxicity against normal cells that also carry that marker, and can allow tumor cells that lose the antigen to escape treatment. By engineering the CAR T cell to recognize both CD38 and CLL-1, the therapy aims to improve tumor specificity and reduce the chance that leukemic cells survive by losing just one target. This dual-antigen strategy is broadly relevant to hematologic malignancies where no single surface marker is both highly specific and uniformly expressed on all malignant cells.