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2-23 CAR NK cells are an investigational, off-the-shelf cellular immunotherapy consisting of cord blood-derived natural killer (NK) cells engineered to express a chimeric antigen receptor (CAR) targeting C-type lectin-like molecule 1 (CLL-1/CLEC12A). Developed by researchers at MD Anderson Cancer Center, the construct utilizes a novel high-affinity monoclonal antibody (scFv clone 2-23) coupled with CD28 and CD3ζ signaling domains. To enhance persistence and expansion, the cells are also engineered to co-express IL-15 via a T2A linker. CLL-1 is a prominent target in acute myeloid leukemia (AML) as it is highly expressed on AML blasts and leukemic stem cells while being absent on healthy hematopoietic stem cells. Preclinical studies demonstrate that 2-23 CAR NK cells exhibit superior antigen sensitivity and cytotoxicity compared to earlier CLL-1 CAR constructs (such as the M26 clone), particularly against targets with low antigen density, and show robust anti-leukemic activity in xenograft and patient-derived xenograft (PDX) models.
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