Natural killer cell immunotherapy: from bench to bedside

The potential of natural killer (NK) cells to target numerous malignancies in vitro has been well documented; however, only limited success has been seen in the clinic. Although NK cells prove non-toxic and safe regardless of the cell numbers injected, there is often little persistence and expansion observed in a patient, which is vital for mounting an effective cellular response. NK cells can be isolated directly from peripheral blood, umbilical cord blood, or bone marrow, expanded in vitro using cytokines or differentiated in vitro from hematopoietic stem cells. Drugs that support NK cell function such as lenalidomide and bortezomib have also been studied in the clinic, however, the optimum combination, which can vary among different malignancies, is yet to be identified. NK cell proliferation, persistence, and function can further be improved by various activation techniques such as priming and cytokine addition though whether stimulation pre- or post-injection is more favorable is another obstacle to be tackled. Here, we review the various methods of obtaining and activating NK cells for use in the clinic while considering the ideal product and drug complement for the most successful cellular therapy.