Therapeutic effects of NK cell-derived EVs on cancer: Current advances and future treatment strategies

Cancer remains a leading cause of death globally, with conventional treatments such as surgery, chemotherapy, and radiotherapy offering limited success, especially in advanced stages or cases with metastatic or resistant tumors. As a result, there is a pressing need for novel therapeutic approaches. Immunotherapy has emerged as a promising alternative, with natural killer (NK) cells playing a central role due to their ability to selectively target and kill cancer cells while sparing healthy tissues. This review explores the therapeutic potential of NK cell-derived extracellular vesicles (NK-EVs), a promising innovation in cancer treatment. NK-EVs, including exosomes, carry bioactive molecules such as proteins, lipids, and RNA that can influence tumor cells and the surrounding immune microenvironment. The review examines the various sources of NK-EVs, their biological functions, and the mechanisms through which they exert their therapeutic effects, focusing on both their membrane and content proteins. These vesicles play a crucial role in immune modulation, including enhancing immune responses and promoting apoptosis in cancer cells. Additionally, NK-EVs have gained attention as potential carriers for delivering therapeutic agents, such as chemotherapeutic drugs, small interfering RNAs (siRNAs), and microRNAs (miRNAs), providing a novel approach for overcoming the limitations of traditional cancer therapies, such as poor drug delivery and resistance. The review also highlights recent advances in NK-EV production, including bioreactor-based systems and stress-induced EV generation, which are essential for scaling up their use in clinical applications. Furthermore, we discuss the immunotherapeutic effects of NK-EVs and NK exosomes (Exos), the methods for assessing their cytotoxicity, and their potential to serve as effective carriers for targeted therapy. By reviewing current advancements and future strategies, this article provides a comprehensive outlook on NK-EVs as a promising tool in the fight against cancer, offering novel pathways for more effective and targeted cancer therapies.