Allogeneic (non-HLA-matched donor-derived) natural killer (NK) cell

Class

Allogeneic (non-HLA-matched donor-derived) natural killer (NK) cell therapy — unmodified/non-CAR, relies on innate NK cytolytic activity against physiologically stressed tumor cells rather than a defined antigen receptor

Notes

original target text: Allogeneic (non-HLA-matched donor-derived) natural killer (NK) cell therapy — unmodified/non-CAR, relies on innate NK cytolytic activity against physiologically stressed tumor cells rather than a defined antigen receptor

Natural killer (NK) cells are innate immune lymphocytes that kill abnormal cells—virally infected or malignant—without needing to recognize a specific tumor antigen the way T cells do. Their activity is set by a balance of activating receptors, which detect stress-induced ligands on unhealthy cells, and inhibitory receptors, which sense normal levels of major histocompatibility complex (MHC) class I ("self") molecules on healthy tissue. When MHC class I is reduced or absent, a common feature of many cancer cells, this inhibitory signal is lost and the NK cell releases cytotoxic granules containing perforin and granzymes, killing the target. Allogeneic NK cell therapy uses NK cells collected from a healthy donor rather than the patient, and deliberately does not require matching the donor's tissue type (HLA) to the recipient's. Because NK cell reactivity, unlike T cell reactivity, is not restricted by HLA matching in the same way, mismatched donor NK cells can be administered without triggering the severe graft-versus-host disease seen with mismatched T cells, while potentially gaining added anti-tumor activity from HLA mismatch itself. This approach broadly matters in hematologic cancers and is being explored in solid tumors, offering a scalable, off-the-shelf cellular therapy option distinct from patient-specific approaches.