In cancer treatment, traditional therapies are limited, and T-cell therapies are faced with challenges such as high costs and toxicity. As a mainstay of innate immunity, natural killer (NK) cells offer distinct advantages, including the ability to kill target cells without antigen sensitization, a low risk of graft-versus-host disease (GVHD), and the potential for "off-the-shelf" application. This review summarizes recent advancements in NK cell-based therapies, focusing on in vitro amplification strategies and genetic engineering modifications. Key findings include: cytokine and feeder layer co-culture systems have been shown to expand NK cells over 500-fold; CD19-targeted chimeric antigen receptor (CAR)-NK cells exhibit a 50%-70% response rate in B-cell lymphoma patients; CRISPR-mediated gene editing enhances cytotoxicity against solid tumors; nanoparticle-based delivery systems improve tumor infiltration of NK cells; and allogeneic NK cell therapy carries a near-zero GVHD risk. Notably, significant challenges persist, such as the immunosuppressive tumor microenvironment, poor in vivo persistence of NK cells, congenital functional defects, potential off-target effects of CAR-NK cells, and the lack of standardized production protocols. While NK cell therapy demonstrates substantial promise in cancer immunotherapy, overcoming these bottlenecks is essential for its broader clinical translation and application.
Jun Chen (Tue,) studied this question.