Abstract
Regulatory T (Treg) cells are a suppressive subset of CD4+ T cells that maintain immune homeostasis and restrain inflammation. Three decades after their discovery, the promise of strategies to harness Treg cells for therapy has never been stronger. Multiple clinical trials seeking to enhance endogenous Treg cells or deliver them as a cell-based therapy have been performed and hint at signs of success, as well as to important limitations and unanswered questions. Strategies to deplete Treg cells in cancer are also in active clinical testing. Furthermore, multi-dimensional methods to interrogate the biology of Treg cells are leading to a refined understanding of Treg cell biology and new approaches to harness tissue-specific functions for therapy. A new generation of Treg cell clinical trials is now being fuelled by advances in nanomedicine and synthetic biology, seeking more precise ways to tailor Treg cell function. This Review will discuss recent advances in our understanding of human Treg cell biology, with a focus on mechanisms of action and strategies to assess outcomes of Treg cell-_targeted therapies. It highlights results from recent clinical trials aiming to enhance or inhibit Treg cell activity in a variety of diseases, including allergy, transplantation, autoimmunity and cancer, and discusses ongoing strategies to refine these approaches.
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Acknowledgements
The authors’ work in this area is funded by the Canadian Institutes for Health Research (CIHR; FDN-154304), Juvenile Diabetes Research Foundation Canada (3-COE-2022-1103-M-B), U.S. Department of Defense/Reconstructive Transplant Research Program (HT94252310626), and the Leona M. and Harry B. Helmsley Charitable Trust. C.M.W. is supported by a CIHR doctoral award. D.A.B. was supported by fellowships from the CIHR and Michael Smith Health Research BC. M.K.L. is Canada Research Chair in Immune Engineering and receives a Scientist Salary Award from the BC Children’s Hospital Research Institute. We thank K. Salim for providing sample flow plots displayed in Fig. 2.
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C.M.W. and M.K.L. conceived the article. All authors contributed to the research, writing and editing of the manuscript.
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M.K.L. is a science advisory board member for Anokion, advises for and holds shares in Integrated Nanotherapeutics, and is an inventor on patent applications related to A2-chimaeric antigen receptor regulatory T cells with licensed technology to Sangamo Therapeutics. C.M.W. and D.A.B. declare no competing interests.
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Wardell, C.M., Boardman, D.A. & Levings, M.K. Harnessing the biology of regulatory T cells to treat disease. Nat Rev Drug Discov (2024). https://doi.org/10.1038/s41573-024-01089-x
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DOI: https://doi.org/10.1038/s41573-024-01089-x
