ONKT104

ONKT104 is an investigational, dual-targeted natural killer (NK) cell therapy being developed for the treatment of acute myeloid leukemia (AML). It is engineered to express a chimeric antigen receptor (CAR) targeting C-type lectin domain family 12 member A (CLEC12A, also known as CLL-1), a leukemic stem cell antigen selectively expressed on AML cells but not on normal hematopoietic stem cells, thereby reducing the risk of toxicity to healthy bone marrow. In addition, ONKT104 incorporates a proprietary high-affinity variant of TNF-related apoptosis-inducing ligand (TRAILv) that targets death receptor 4 (DR4), enabling engagement of both intrinsic and extrinsic apoptotic pathways in cancer cells. This dual-targeting approach aims to enhance anti-leukemic efficacy and reduce the likelihood of tumor escape due to antigen loss. The therapy is designed as an off-the-shelf product using optimally engineered NK cells with additional modifications such as CISH knockout and scIL-15 expression to improve persistence and function[1][2][4][5][6][8].