Review 10.1172/JCI129338

Killers 2.0: NK cell therapies at the forefront of cancer control

Jonathan J. Hodgins,1,2 Sarwat T. Khan,1 Maria M. Park,1,2 Rebecca C. Auer,1,3 and Michele Ardolino1,2

1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

2Department of Biochemistry, Microbiology and Immunology, and

3Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Address correspondence to: Michele Ardolino, 501 Smyth Road, Cancer Center, 3-328, Ottawa, Ontario K1H8M2, Canada. Phone: 613.737.8899 ext. 77257; Email: m.ardolino@uottawa.ca.

Authorship note: JJH and STK equally contributed to this manuscript.

Find articles by Hodgins, J. in: JCI | PubMed | Google Scholar |

1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

2Department of Biochemistry, Microbiology and Immunology, and

3Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Address correspondence to: Michele Ardolino, 501 Smyth Road, Cancer Center, 3-328, Ottawa, Ontario K1H8M2, Canada. Phone: 613.737.8899 ext. 77257; Email: m.ardolino@uottawa.ca.

Authorship note: JJH and STK equally contributed to this manuscript.

Find articles by Khan, S. in: JCI | PubMed | Google Scholar

1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

2Department of Biochemistry, Microbiology and Immunology, and

3Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Address correspondence to: Michele Ardolino, 501 Smyth Road, Cancer Center, 3-328, Ottawa, Ontario K1H8M2, Canada. Phone: 613.737.8899 ext. 77257; Email: m.ardolino@uottawa.ca.

Authorship note: JJH and STK equally contributed to this manuscript.

Find articles by Park, M. in: JCI | PubMed | Google Scholar

1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

2Department of Biochemistry, Microbiology and Immunology, and

3Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Address correspondence to: Michele Ardolino, 501 Smyth Road, Cancer Center, 3-328, Ottawa, Ontario K1H8M2, Canada. Phone: 613.737.8899 ext. 77257; Email: m.ardolino@uottawa.ca.

Authorship note: JJH and STK equally contributed to this manuscript.

Find articles by Auer, R. in: JCI | PubMed | Google Scholar |

1Centre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

2Department of Biochemistry, Microbiology and Immunology, and

3Department of Surgery, University of Ottawa, Ottawa, Ontario, Canada.

Address correspondence to: Michele Ardolino, 501 Smyth Road, Cancer Center, 3-328, Ottawa, Ontario K1H8M2, Canada. Phone: 613.737.8899 ext. 77257; Email: m.ardolino@uottawa.ca.

Authorship note: JJH and STK equally contributed to this manuscript.

Find articles by Ardolino, M. in: JCI | PubMed | Google Scholar |

First published September 3, 2019 - More info

Published in Volume 129, Issue 9 on September 3, 2019
J Clin Invest. 2019;129(9):3499–3510. https://doi.org/10.1172/JCI129338.
© 2019 American Society for Clinical Investigation
First published September 3, 2019 - Version history

Natural killer (NK) cells are innate cytotoxic lymphocytes involved in the surveillance and elimination of cancer. As we have learned more and more about the mechanisms NK cells employ to recognize and eliminate tumor cells, and how, in turn, cancer evades NK cell responses, we have gained a clear appreciation that NK cells can be harnessed in cancer immunotherapy. Here, we review the evidence for NK cells’ critical role in combating transformed and malignant cells, and how cancer immunotherapies potentiate NK cell responses for therapeutic purposes. We highlight cutting-edge immunotherapeutic strategies in preclinical and clinical development such as adoptive NK cell transfer, chimeric antigen receptor–expressing NK cells (CAR-NKs), bispecific and trispecific killer cell engagers (BiKEs and TriKEs), checkpoint blockade, and oncolytic virotherapy. Further, we describe the challenges that NK cells face (e.g., postsurgical dysfunction) that must be overcome by these therapeutic modalities to achieve cancer clearance.

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