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NK Cell-based Immunotherapies in Pediatric Oncology

McDowell, Kimberly A. MD, PhD; Hank, Jacquelyn A. PhD; DeSantes, Kenneth B. MD; Capitini, Christian M. MD; Otto, Mario MD, PhD; Sondel, Paul M. MD, PhD

Journal of Pediatric Hematology/Oncology: March 2015 - Volume 37 - Issue 2 - p 79–93
doi: 10.1097/MPH.0000000000000303
Review Article

The past decade has seen several anticancer immunotherapeutic strategies transition from “promising preclinical models” to treatments with proven clinical activity or benefit. In 2013, the journal Science selected the field of Cancer Immunotherapy as the overall number-1 breakthrough for the year in all of scientific research. In the setting of cancer immunotherapy for adult malignancies, many of these immunotherapy strategies have relied on the cancer patient’s endogenous antitumor T-cell response. Although much promising research in pediatric oncology is similarly focused on T-cell reactivity, several pediatric malignancies themselves, or the chemo-radiotherapy used to achieve initial responses, can be associated with profound immune suppression, particularly of the T-cell system. A separate component of the immune system, also able to mediate antitumor effects and less suppressed by conventional cancer treatment, is the NK-cell system. In recent years, several distinct immunotherapeutic approaches that rely on the activity of NK cells have moved from preclinical development into clinical testing, and some have shown clear antitumor benefit. This review provides an overview of NK cell-based immunotherapy efforts that are directed toward childhood malignancies, with an emphasis on protocols that are already in clinical testing.

Department of Pediatrics, Division of Pediatric Hematology, Oncology and Bone Marrow Transplant, The University of Wisconsin, Madison, WI

Supported by National Institutes of Health Grants CA032685, CA87025, CA166105, CA14520, GM067386, Department of Defense grant W81XWH-08-1-0559, and grants from the Midwest Athletes for Childhood Cancer Fund, Stand Up to Cancer, St. Baldrick’s Foundation, The Crawdaddy Foundation, The Evan Dunbar Foundation, Alex’s Lemonade Stand Foundation, Hyundai Hope on Wheels, and the University of Wisconsin-Madison Institute for Clinical and Translational Research (ICTR) TL1 Training Grant 1TL1RR025013-01.

The authors declare no conflict of interest.

Reprints: Paul M. Sondel, MD, PhD, 4159 MACC Fund Childhood Cancer Research Wing, WIMR Building, 1111 Highland Ave, Madison, WI 53705 (e-mail:

Received March 21, 2014

Accepted November 21, 2014

Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.