Engineered NK Cells Against Cancer and Their Potential Applications Beyond

Abstract

Cell therapy is an innovative therapeutic concept where viable cells are implanted, infused, or grafted into a patient to treat impaired or malignant tissues. The term was first introduced circa the 19thcentury and has since resulted in multiple breakthroughs in different fields of medicine, such as neurology, cardiology, and oncology. Lately, cell and gene therapy are merging to provide cell products with additional or enhanced properties. In this context, adoptive transfer of genetically modified cytotoxic lymphocytes has emerged as a novel treatment option for cancer patients. To this day, five cell therapy products have been FDA approved, four of which for CD19-positive malignancies and one for B-cell maturation antigen (BCMA)-positive malignancies. These are personalized immunotherapies where patient T cells are engineered to express chimeric antigen receptors (CARs) with the aim to redirect the cells against tumor-specific antigens. CAR-T cell therapies show impressive objective response rates in clinical trials that, in certain instances, may reach up to 80%. However, the life-threatening side effects associated with T cell toxicity and the manufacturing difficulties of developing personalized therapies hamper their widespread use. Recent literature suggests that Natural Killer (NK) cells, may provide a safer alternative and an ‘off-the-shelf’ treatment option thanks to their potent antitumor properties and relatively short lifespan. Here, we will discuss the potential of NK cells in CAR-based therapies focusing on the applications of CAR-NK cells in cancer therapy and beyond.