Human NKG2C+ adaptive NK cells for Cancer immunotherapy.

Natural killer (NK) cells are key components of the innate immune system and play a pivotal role in tumor immunosurveillance. In recent years, a subset of NKG2C+ adaptive NK cells induced by human cytomegalovirus (HCMV) infection has attracted considerable attention because of its distinctive memory-like properties. This subset has shown substantial therapeutic potential in preclinical models of both haematological malignancies and solid tumors, and early-phase clinical trials in acute myeloid leukaemia (AML) and ovarian cancer have indicated a favorable safety profile with preliminary signs of efficacy. By applying a "super-donor" selection strategy and combining NKG2C-specific activation with cytokine stimulation, efficient ex vivo expansion of NKG2C+ adaptive NK cells can be achieved. When further integrated with synthetic immunology approaches-such as NK cell engagers (NKCEs) or engineered receptors-together with epigenetic modulation and metabolic reprogramming, the antitumor functions of this subset can be comprehensively augmented. These advances may unlock its therapeutic potential and offer new directions and paradigms for next-generation cancer immunotherapy.