New Orders to an Old Soldier: Optimizing NK Cells for Adoptive Immunotherapy in Hematology.

NK (Natural Killer) cell-mediated adoptive immunotherapy has gained attention in hematology due to the progressing knowledge of NK cell receptor structure, biology and function. Today, challenges related to NK cell expansion and persistence in vivo as well as low cytotoxicity have been mostly overcome by pioneering trials that focused on harnessing NK cell functions. Recent technological advancements in gene delivery, gene editing and chimeric antigen receptors (CARs) have made it possible to generate genetically modified NK cells that enhance the anti-tumor efficacy and represent suitable "off-the-shelf" products with fewer side effects. In this review, we highlight recent advances in NK cell biology along with current approaches for potentiating NK cell proliferation and activity, redirecting NK cells using CARs and optimizing the procedure to manufacture clinical-grade NK and CAR NK cells for adoptive immunotherapy.