Preclinical studies of chimeric antigen receptor-modified natural killer cells in cancer immunotherapy: a review

Introduction As one of the most efficacious methods of cancer immunotherapy, chimeric antigen receptor-modified immune cells have recently drawn enormous attention. After the great success achieved with CAR-T-cells in cancer treatment both in preclinical setting and in the clinic, other types of immune cells, including natural killer (NK)-cells and macrophages, have been evaluated for their anti-cancer effects along with their potential superiority against CAR-T-cells, especially in terms of safety. First introduced by Tran et al. almost 26 years ago, CAR-NK-cells are now being considered as efficient immunotherapeutic modalities in various types of cancers, not only in preclinical setting but also in numerous phase I and II clinical studies. Areas Covered In this review, we aim to provide a comprehensive survey of the preclinical studies on CAR-NK-cells' development, with an evolutional approach on CAR structures and their associated signaling moieties. Current NK-cell sources and modes of gene transfer are also reviewed. Expert Opinion CAR-NK-cells have appeared as safe and effective immunotherapeutic tools in preclinical settings; however, designing CAR structures with an eye on their specific biology, along with choosing the optimal cell source and gene transfer method require further investigation to support clinical studies.