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Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors

1
Chaum Life Center, CHA University School of Medicine, Seoul 06062, Korea
2
Graduate school of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, Korea
3
Department of Gastroenterology and Hepatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13496, Korea
4
Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Korea
5
School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(10), 1534; https://doi.org/10.3390/cancers11101534 (registering DOI)
Received: 2 July 2019 / Revised: 29 September 2019 / Accepted: 6 October 2019 / Published: 11 October 2019
In treatments of solid tumors, adoptive transfer of ex vivo expanded natural killer (NK) cells has dawned as a new paradigm. Compared with cytotoxic T lymphocytes, NK cells take a unique position targeting tumor cells that evade the host immune surveillance by down-regulating self-antigen presentation. Recent findings highlighted that NK cells can even target cancer stem cells. The efficacy of allogeneic NK cells has been widely investigated in the treatment of hematologic malignancies. In solid tumors, both autologous and allogeneic NK cells have demonstrated potential efficacy. In allogeneic NK cell therapy, the mismatch between the killer cell immunoglobulin-like receptor (KIR) and human leukocyte antigen (HLA) can be harnessed to increase the antitumor activity. However, the allogeneic NK cells cause more adverse events and can be rejected by the host immune system after repeated injections. In this regard, the autologous NK cell therapy is safer. This article reviews the published results of clinical trials and discusses strategies to enhance the efficacy of the NK cell therapy. The difference in immunophenotype of the ex vivo expanded NK cells resulted from different culture methods may affect the final efficacy. Furthermore, currently available standard anticancer therapy, molecularly targeted agents, and checkpoint inhibitors may directly or indirectly enhance the efficacy of NK cell therapy. A recent study discovered that NK cell specific genetic defects are closely associated with the tumor immune microenvironment that determines clinical outcomes. This finding warrants future investigations to find the implication of NK cell specific genetic defects in cancer development and treatment, and NK cell deficiency syndrome should be revisited to enhance our understanding. Overall, it is clear that NK cell therapy is safe and promises a new paradigm for the treatment of solid tumors. View Full-Text
Keywords: immunotherapy; natural killer; autologous; allogeneic; NK cell deficiency immunotherapy; natural killer; autologous; allogeneic; NK cell deficiency
MDPI and ACS Style

Oh, S.; Lee, J.-H.; Kwack, K.; Choi, S.-W. Natural Killer Cell Therapy: A New Treatment Paradigm for Solid Tumors. Cancers 2019, 11, 1534.

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