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REVIEW article

Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1436968
This article is part of the Research Topic Cognate recognition, functional properties and immunotherapeutic applications of iNKT cells: leveling the road to the clinic View all articles

Traversing the Bench to Bedside Journey for iNKT Cell Therapies

Provisionally accepted
Julie O'Neal Julie O'Neal 1,2Melissa Mavers Melissa Mavers 2,3Reyka Jayasinghe Reyka Jayasinghe 1John F. DiPersio John F. DiPersio 1,2*
  • 1 Division of Oncology, Washington University School of Medicine in Saint Louis, Saint Louis, United States
  • 2 Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, Washington, United States
  • 3 Division of Hematology and Oncology, Department of Pediatrics, Washington University School of Medicine in S, t. Louis, United States

The final, formatted version of the article will be published soon.

    Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft versus host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti-cancer efficacy.Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting.

    Keywords: invariant natural killer T cell, iNKT, Chimeric Antigen Receptor, CAR, graft versus host disease, GvHD, immune cells, Clinical Trial

    Received: 22 May 2024; Accepted: 24 Jul 2024.

    Copyright: © 2024 O'Neal, Mavers, Jayasinghe and DiPersio. 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) or licensor 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: John F. DiPersio, Siteman Cancer Center, School of Medicine, Washington University in St. Louis, St. Louis, 63110, Washington, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.