Natural killer (NK) cells are normal white blood cells capable of killing cancer cells without prior sensitization. Unlike allogeneic T cells, NK cells do not cause graft-vs-host disease. Furthermore, allogeneic NK cell infusions are attractive for cancer therapy because of non–cross-resistant mechanisms of action and minimal overlapping toxicities with standard cancer treatments. Although NK therapy is promising, many obstacles will need to be overcome, including insufficient cell numbers, effector dysfunction, exhaustion, and tumor cell evasion. In this lecture, we will review recent NK cell biology studies and the advancements in biotechnology. We will examine novel approaches of NK cell therapy that may improve therapeutic efficiency and reduce side effects, including immunogenetic-based donor selection, refined NK cell bioprocessing, and novel augmentation techniques, to improve NK cell function and to reduce tumor resistance. Although data from clinical trials are currently limited primarily to hematologic malignancies, broader applications to a wide spectrum of solid cancers are under way. The unique properties of human NK cells may open up a new arena of novel cell-based immunotherapy against cancers that are resistant to contemporary therapies.
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