Advances in NK cell therapy for hematologic malignancies: NK source, persistence and tumor targeting.

Natural Killer (NK) cells yield promise in therapy of hematologic malignancies. The clinical experience with adoptively transferred allogeneic NK cells over past two decades has revealed safety and minimal risk of CRS or ICANS. Unlike T cells which have to be genetically altered to avoid graft vs host disease (GVHD), HLA mismatched NK cells can be infused without GVHD risk. This makes them ideal for the development of off-the-shelf products. In this review we focus on NK biology relevant to the cancer therapy, the trajectory of NK therapeutics for leukemia, lymphoma, and myeloma; and advantages of the NK cell platform. We will also discuss novel methods to enhance NK cell targeting, persistence, and function in the tumor microenvironment. The future of NK cell therapy depends on novel strategies to realize these qualities.