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Unengineered NK cells are natural killer cells that have not been genetically modified to express chimeric antigen receptors (CARs) or other exogenous proteins. These cells are typically isolated from allogeneic sources, such as peripheral blood or umbilical cord blood, and expanded ex vivo before being infused into patients as a form of adoptive cell therapy. They rely on their innate repertoire of activating and inhibitory receptors, including killer cell immunoglobulin-like receptors (KIRs), NKG2D, and natural cytotoxicity receptors (NCRs), to recognize and eliminate malignant or virally infected cells. In clinical and preclinical development, unengineered NK cells are frequently used as a standalone immunotherapy or as a critical control arm to benchmark the enhanced specificity, persistence, and anti-tumor activity of engineered cell therapies like CAR-NK cells.
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