Harnessing the immunotherapeutic potentials of gamma delta T cells against hematological malignancies
Author(s)
Agbuduwe, Charles
Maher, John
Anderson, John
Type
Journal Article
Abstract
Gamma delta (γδ) T cells, which constitute about 5%–10% of peripheral blood lymphocytes, play key roles in tumor immunosurveillance and are often enriched within epithelial tissues. They are unique in their Major Histocompatibility Complex-independent antigen recognition via the γδ T-cell receptor (TCR) as well as via innate receptors, making them ideal1 candidates for allogeneic “off-the-shelf” cell therapy products. In humans, two main structural subsets of γδ T cells—Vδ1 and Vδ2—have been defined, which differ in TCRδ chains, effector function, and tissue localizations. Vδ2 T cells constitute the majority of γδ T cells in peripheral blood and can be expanded with aminobisphosphonates such as zoledronic acid. In recent years, the potent antitumor functions of Vδ1 T cells have also been recognized, and new expansion protocols are being developed. Given the ample preclinical evidence of γδ T-cell efficacy against hematological malignancies, several γδ T-cell-based cell therapy products are currently in clinical development, and there has been an exponential increase in the number of adoptive γδ T-cell therapy clinical trials. This comprehensive review provides an overview of the rationale for γδ T-cell therapy, ongoing clinical trials, as well as the challenges and future role of γδ T-cell-based immune therapies in hematology.
Date Issued
2025-08-01
Date Acceptance
2025-07-02
Citation
HemaSphere, 2025, 9 (8)
ISSN
2572-9241
Publisher
Wiley
Journal / Book Title
HemaSphere
Volume
9
Issue
8
Copyright Statement
© 2025 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Article Number
e70182
Date Publish Online
2025-08-07