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Cancer cell cytotoxicity via engineered natural killer (NK) cell activity refers to the targeted destruction of cancer cells by NK cells that have been genetically modified or otherwise enhanced to improve their ability to recognize and kill tumor cells. Engineering these cells—often through chimeric antigen receptor (CAR) technology—aims to boost their specificity, persistence, and potency against cancer. NK cells naturally surveil for abnormal or stressed self-cells, including tumorigenic or virally infected targets. They induce apoptosis in these targets primarily through release of lytic granules containing perforin and granzymes and/or engagement of death receptors on target cells via ligands such as FasL or TRAIL. Upon activation, NK cells secrete cytokines like TNFα and IFNγ that modulate the immune response. Engineered CAR-NK therapies are being developed as alternatives or complements to CAR-T therapies. They offer potential advantages such as reduced risk of graft-versus-host disease and cytokine release syndrome. Both hematological malignancies (e.g., leukemias/lymphomas) and solid tumors can be targeted using appropriately designed CAR-NK constructs.
Engineered NK cells recognize and bind to tumor-specific antigens, leading to the release of cytotoxic granules (perforin, granzymes) and/or the activation of death receptors (FasL, TRAIL), ultimately inducing apoptosis in cancer cells.
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