Cancer is still one of the most common causes of death around the world, and problems with traditional treatments, such as toxicity, resistance, and relapse, have led to the creation of immunotherapeutic strategies. Among these, natural killer (NK) cells have emerged as a promising platform due to their innate ability to recognize and eliminate tumor cells without prior sensitization and without major histocompatibility complex (MHC) restriction. This review presents a full picture of the latest developments in NK cell biology and engineering for cancer immunotherapy. It describes the main ways in which NK cells can be activated, kill other cells, and change the immune system, as well as their main sources, which are peripheral blood, cord blood, NK-92 cell lines, and NK cells created from induced pluripotent stem cells. Recent advancements in genetic engineering, notably chimeric antigen receptor (CAR)-NK cells, cytokine armoring, and CRISPR-based gene editing, have markedly improved NK cell specificity, durability, and antitumor efficacy. Emerging methodologies, including synthetic biology, nanotechnology-based delivery systems, and metabolic reprogramming, are enhancing resistance to the immunosuppressive tumor microenvironment (TME). Preliminary clinical trials indicate promising efficacy and a favorable safety profile relative to CAR-T cell therapies, especially in hematological malignancies. Even with these improvements, problems still remain, such as limited in vivo persistence, poor tumor infiltration, and complicated manufacturing processes. Continued integration of advanced engineering strategies and clinical optimization is expected to position NK cell-based therapies as a key component of next-generation cancer immunotherapy.
Sumit Sharma (Sun,) studied this question.