Dark NKnight rising: a current perspective on NK cell and CAR-NK cell therapy

Abstract

Natural killer (NK) cell therapy began decades ago with administration of small doses of minimally-characterized cells known as cytokine-induced or lymphokine-activated killer cells (CIK or LAK, respectively). Methods and conditions that enabled the broad adoption of T cell therapies have often been less effective for NK cells, but in the last 15 years, new NK-specific advances in selection, differentiation, and ex vivo expansion hav e made possible the infusion of large doses of pure and potent NK cell products. Also, NK cells have been more resistant to the genetic modification approaches utilized for engineering T cells, but in the last 5 years several robust approaches for NK cell modification have advanced to the clinic. Thus, a tremendous surge in NK cell clinical trials has been seen recently. Here, we present a focused perspective on the key developments in NK cell therapy that differentiate it from T cell therapies and discuss areas that are key to their clinical and commercial success- both current advancements and hurdles that remain to be addressed.

Keywords: cellular therapy; chimeric antigen receptor; clinical trials; gene editing.