The clinical success stories of chimeric antigen receptor (CAR)-T cell therapy against B-cell malignancies have contributed to immunotherapy being at the forefront of cancer therapy today. Their success has fueled interest in improving CAR constructs, identifying additional antigens to target, and clinically evaluating them across a wide range of malignancies. However, along with the exciting potential of CAR-T therapy comes the real possibility of serious side effects. While the FDA has approved commercialized CAR-T cell therapy, challenges associated with manufacturing, costs, and related toxicities have resulted in increased attention being paid to implementing CAR technology in innate cytotoxic natural killer (NK) cells. Here, we review the current landscape of the CAR-NK field, from successful clinical implementation to outstanding challenges which remain to be addressed to deliver the full potential of this therapy to more patients.
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