Advances in pluripotent stem cell-derived natural killer cells for cancer immunotherapy

Abstract Adoptive cell therapy using natural killer (NK) cells is rapidly emerging as a promising method to treat a variety of malignancies. NK cells can now be routinely derived in vitro from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs). An iPSC-based platform to generate NK cells for adoptive therapy overcomes a number of constraints associated with the use of other available NK cell sources for generating uniform, genetically engineered NK cell therapy products with enhanced activity. iPSC-derived NK cells can now be produced at a clinical scale, and within the last few years several genetically engineered iPSC-NK cell products have entered clinical trials to treat cancer, underscoring their therapeutic potential. Here we review current progress made in the generation of NK cells from hESCs and iPSCs, including key studies identifying novel strategies to generate genetically modified iPSC-derived NK cells with augmented antitumor function and improved therapeutic efficacy, and explore iPSC-derived NK cell products that are currently being evaluated in clinical trials.