Chimeric antigen receptor (CAR)-modified NK cells against cancer: Opportunities and challenges

Abstract NK cells may have great potential in tumor immunotherapy because they can kill tumor cells directly and quickly. Chimeric antigen receptor is a fusion protein composed of extracellular antigen recognition domain, transmembrane domain and intracellular signal domain. Rapid development of CAR-modified T cells has made tremendous achievements in the treatment of malignancies, especially hematological malignancies. However, there are many deficiencies in clinical application of CAR-T cell therapy. Car-modified NK cells have attracted much attention because they may avoid these shortcomings. At present, preclinical and clinical studies have shown that CAR-NK cell therapy may play significant anti-tumor role and it is safer than CAR-T cell therapy. Nevertheless, CAR-NK cell therapy still faces some challenges, such as the expansion and activation of primary NK cells in vitro, the difficulty to store and ship NK cell products and the low transduction efficiency. Thus further research is still needed to optimize CAR-NK cell therapy. Building better CAR-NK cells is important to improve the treatment efficacy and combination therapy offers a novel direction of NK-cell based immunotherapy.