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NKT Cells in Cancer Immunotherapy

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Front. Immunol. | doi: 10.3389/fimmu.2018.00384

Novel Approaches to Exploiting invariant NKT cells in Cancer Immuno-Therapy

  • 1Gastroentrerology, Brigham & Women's Hospital, Harvard Medical School, United States
  • 2Agenus (United States), United States
  • 3University of Manchester, United Kingdom

iNKT cells are a subset of innate-like T cells that utilize an invariant TCR alpha chain complexed with a limited repertoire of TCR beta chains to recognize specific lipid antigens presented by CD1d molecules. Because iNKT cells have an invariant TCR they can be easily identified and targeted in both humans and mice via standard reagents, making this a population of T cells that has been well characterized. It has been shown that iNKT cells are some of the first cells to respond during infection with a pathogen and the type of cytokines that iNKT cells make help determine the type of immune response that develops in various situations. Indeed, along with immunity to pathogens, pre-clinical mouse studies have clearly demonstrated that iNKT cells play a critical role in tumor immunosurveillance. They can mediate anti-tumor immunity by direct recognition of tumor cells that express CD1d, and/or via targeting CD1d found on cells within the tumor microenvironment. Multiple groups are now working on manipulating iNKT cells for clinical benefit within the context of cancer, and have demonstrated that targeting iNKT cells can have a therapeutic benefit in patients. In this review, we will briefly introduce iNKT cells, then discuss preclinical data on roles of iNKT cells and clinical trials that have targeted iNKT cells in cancer patients. We finally discuss how future trials could be modified to further increase the efficacy of iNKT cell therapies, in particular CAR-iNKT and rTCR-iNKT cells.

Keywords: NKT cells, CD1d, iNKT cells, cancer immunotherapy, Monoclonal antibody (mAb)

Received: 02 Nov 2017; Accepted: 12 Feb 2018.

Edited by:

Weiming Yuan, University of Southern California, United States

Reviewed by:

S.M. Mansour Haeryfar, University of Western Ontario, Canada
Leonid Metelitsa, Baylor College of Medicine, United States  

Copyright: © 2018 Exley, Wolf and Choi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Mark A. Exley, Brigham & Women's Hospital, Harvard Medical School, Gastroentrerology, 75 Francis St., Boston, 02115, MA, United States,