Abstract
Natural killer (NK) cell‑based immunotherapy has emerged as a transformative approach for cancer treatment However, its widespread clinical application faces several challenges, such as donor variability, limited scalability and functional heterogeneity of primary NK cells. Additionally, issues including in vivo persistence, resistance to tumor microenvironment and safety concerns related to genomic instability further hinder its clinical application. Induced pluripotent stem cell (iPSC)‑derived NK cells offer a promising solution. They provide high homogeneity and quality control, genetic engineering flexibility and inexhaustible cell source. This present review highlighted the unique advantages of iPSC‑ NK cells, including clonal uniformity, enhanced cytotoxicity and suitability for large‑scale production, positioning them as an ideal 'off‑the‑shelf' therapeutic platform. It discussed the biological properties of iPSC‑derived NK cells, advances in differentiation protocols and strategies to augment their anti‑tumor efficacy through genetic engineering, such as chimeric antigen receptor integration and cytokine optimization. Despite these advantages, several challenges remain, including the need to optimize differentiation efficiency, ensure the safety of gene editing (such as off‑target effects) and improve the in vivo migration and infiltration abilities. With technological advances and clinical validation, this present review aimed to guide future research toward overcoming these barriers to clinical implementation. Ultimately, it is expected that iPSC‑NK will become a core means of next‑generation immunotherapy, promoting the combination of personalized and inclusive cancer treatment.