CIR-ILT4.MyD88.DAP10

CIR-ILT4.MyD88.DAP10 is an experimental chimeric ILT receptor (CIR) Natural Killer (NK) cell therapy developed by NKILT Therapeutics. The therapy is designed to target Human Leukocyte Antigen-G (HLA-G), an immune checkpoint molecule often overexpressed in various cancers, including acute myeloid leukemia (AML) and solid tumors like bladder cancer, to evade immune detection. The CIR construct features the extracellular binding domain of Immunoglobulin-like transcript 4 (ILT4/LILRB2) fused to the intracellular signaling domains of MyD88 and DAP10. This configuration converts the normally inhibitory HLA-G/ILT4 interaction into a potent stimulatory signal, enhancing NK cell-mediated tumor cell killing, proliferation, and interferon-gamma (IFN-γ) secretion. Preclinical studies have demonstrated specific activity against HLA-G+ leukemic and solid tumor cells with minimal toxicity toward normal primary human cells.