CLL-1 (CLEC12A)

Class

Autologous CAR T-cell therapy (anti-CLL-1 chimeric antigen receptor)

Pathway

CAR-mediated T-cell recognition and killing of CLL-1-positive leukemic blasts

CLL-1, also called CLEC12A, is a cell-surface protein belonging to the C-type lectin receptor family, found on the surface of myeloid leukemic cells, including the leukemic stem cells thought to sustain acute myeloid leukemia (AML) and drive relapse after treatment. Because CLL-1 is expressed broadly across the leukemic cell hierarchy but is largely absent from normal blood-forming stem cells, it is considered a rational target for therapies designed to eliminate malignant myeloid cells while sparing the healthy stem cell pool needed to regenerate normal blood. Chimeric antigen receptor (CAR) T-cell therapy directed against CLL-1 works by genetically engineering a patient's own T lymphocytes to express a synthetic receptor that recognizes CLL-1 on the surface of leukemic cells. Upon binding, the CAR triggers T-cell activation, proliferation, and cytotoxic killing of the target cell, independent of the T cell's natural antigen receptor. This approach is being explored primarily in AML, a disease where achieving durable remission has been difficult with conventional chemotherapy, and where targeting stem-like leukemic populations is viewed as important for preventing disease recurrence.