Due to their efcient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modifed to obtain capable efector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modifed NK cells. These promising develop-ments assist scientists and physicians to design better applications of NK cells in clinical therapy. Notably, redirecting NK cells using CARs holds important promise for cancer immunotherapy. Various preclinical and a limited number of clinical studies using CAR-NK cells show promising results: efcient elimination of target cells without side efects,such as cytokine release syndrome and neurotoxicity which are seen in CAR-T therapies. In this review, we focus on the details of CAR-NK technology, including the design of efcient and safe CAR constructs and associated NK cell engineering techniques: the vehicles to deliver the CAR-containing transgene, detection methods for CARs, as well as NK cell sources and NK cell expansion. We summarize the current CAR-NK cell literature and include valuable lessons learned from the CAR-T cell feld. This review also provides an outlook on how these approaches may transform cur-rent clinical products and protocols for cancer treatment.
Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy pdf download
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