Viral infections persist as a significant cause of morbidity and mortality worldwide. Conventional therapeutic approaches often fall short in fully eliminating viral infections, primarily due to the emergence of drug resistance. Natural killer (NK) cells, one of the important members of the innate immune system, possess potent immunosurveillance and cytotoxic functions, thereby playing a crucial role in the host's defense against viral infections. Chimeric antigen receptor (CAR)-NK cell therapy has been developed to redirect the cytotoxic function of NK cells specifically towards virus-infected cells, further enhancing their cytotoxic efficacy. In this manuscript, we review the role of NK cells in antiviral infections and explore the mechanisms by which viruses evade immune detection. Subsequently, we focus on the optimization strategies for CAR-NK cell therapy to address existing limitations. Furthermore, we discuss significant advancements in CAR-NK cell therapy targeting viral infections, including those caused by severe acute respiratory syndrome coronavirus 2, human immunodeficiency virus, hepatitis B virus, human cytomegalovirus, and Epstein-Barr virus.
Keywords: CAR-NK cell therapy; NK cell therapy; Optimization strategies; Virus.
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