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**NKG2D ligand-targeting NK cells** are an investigational **CAR-NK cell therapy** in which autologous, allogeneic, or cord blood-derived natural killer cells are engineered to recognize tumor-expressed **NKG2D ligands**. In the earliest reported clinical format, NK cells were **mRNA-electroporated** to transiently express an NKG2D-ligand-directed chimeric antigen receptor for treatment of metastatic solid tumors, particularly metastatic colorectal cancer with peritoneal disease. Related later clinical programs used more durable genetically engineered **NKG2D CAR-NK** products, including constructs co-expressing **membrane-bound interleukin-15** to improve persistence. The therapeutic concept is to redirect NK-cell cytotoxicity toward malignant cells that upregulate stress ligands for NKG2D, thereby promoting tumor-cell killing and cytokine-mediated antitumor immunity. The name provided does not appear to identify a single branded commercial product, but rather a specific investigational NKG2D-ligand-directed NK-cell therapy concept used in early oncology trials.
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