Vikas Yadav* and Deepanshu Kumar
Natural Killer (NK) cells are a distinct subpopulation of innate lymphoid cells with the innate capacity to recognise and destroy cancerous and virally-infected cells. NK cells play a crucial role in anticancer immunity due to their various cytotoxicity mechanisms and capacity to modify the immune response through cytokine production. When NK cells were utilised as immunotherapeutic agents and demonstrated safety and efficacy in the treatment of patients with advanced-stage leukaemia, this role was made clear almost two decades ago. Following the groundbreaking achievements of CAR-engineered adoptive T cell treatment and the development of technologies that can transform cells into potent antitumor weapons, interest in NK cells as a potential immunotherapy option has surged tremendously in recent years. Strategies for the development of NK cell-based therapies emphasise co-stimulatory signalling, checkpoint inhibition, and cytokine armouring to increase NK cell potency and persistence. They also aim to reroute NK cell specificity to the tumour through the expression of CAR or the use of engager molecules. The first generation of NK cell treatments have shown excellent efficacy and amazing safety in the clinic, yielding promising outcomes and igniting strong interest in further research. In this Review, we discuss numerous strategies to increase NK cell cytotoxicity and longevity, assess prospects and obstacles, and consider how the design of future NK cell products will be influenced by the lessons learnt from the clinic and the particular intricacies of each malignancy.