Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Sep 7;22(18):9676.
doi: 10.3390/ijms22189676.

Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges

Mehrdad Hefazi  1 , Sara Bolivar-Wagers  2 , Bruce R Blazar  2
Affiliations
Review

Regulatory T Cell Therapy of Graft-versus-Host Disease: Advances and Challenges

Mehrdad Hefazi et al. Int J Mol Sci. .

Abstract

Graft-versus-host disease (GVHD) is the leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Immunomodulation using regulatory T cells (Tregs) offers an exciting option to prevent and/or treat GVHD as these cells naturally function to maintain immune homeostasis, can induce tolerance following HSCT, and have a tissue reparative function. Studies to date have established a clinical safety profile for polyclonal Tregs. Functional enhancement through genetic engineering offers the possibility of improved potency, specificity, and persistence. In this review, we provide the most up to date preclinical and clinical data on Treg cell therapy with a particular focus on GVHD. We discuss the different Treg subtypes and highlight the pharmacological and genetic approaches under investigation to enhance the application of Tregs in allo-HSCT. Lastly, we discuss the remaining challenges for optimal clinical translation and provide insights as to future directions of the field.

Keywords: GVHD; Treg; allogeneic hematopoietic stem cell transplantation; graft-versus-host disease; regulatory T cells.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

References

    1. Inamoto Y., Martin P.J., Storer B.E., Mielcarek M., Storb R.F., Carpenter P.A. Response endpoints and failure-free survival after initial treatment for acute graft-versus-host disease. Haematologica. 2014;99:385–391. doi: 10.3324/haematol.2013.093062. - DOI - PMC - PubMed
    1. Martin P.J., Rizzo J.D., Wingard J.R., Ballen K., Curtin P.T., Cutler C., Litzow M.R., Nieto Y., Savani B.N., Schriber J.R., et al. First- and second-line systemic treatment of acute graft-versus-host disease: Recommendations of the American Society of Blood and Marrow Transplantation. Biol. Blood Marrow Transplant. 2012;18:1150–1163. doi: 10.1016/j.bbmt.2012.04.005. - DOI - PMC - PubMed
    1. Zeiser R., von Bubnoff N., Butler J., Mohty M., Niederwieser D., Or R., Szer J., Wagner E.M., Zuckerman T., Mahuzier B., et al. Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease. N. Engl. J. Med. 2020;38:1800–1810. doi: 10.1056/NEJMoa1917635. - DOI - PubMed
    1. Cutler C.S., Lee S.J., Arai S., Rotta M., Zoghi B., Lazaryan A., Ramakrishnan A., DeFilipp Z., Salhotra A., Chai-Ho W., et al. Belumosudil for Chronic Graft-versus-Host Disease (cGVHD) After 2 or More Prior Lines of Therapy: The ROCKstar Study. Blood. 2021;136:45–46. doi: 10.1182/blood-2020-139445. - DOI - PMC - PubMed
    1. Miklos D., Cutler C.S., Arora M., Waller E.K., Jagasia M., Pusic I., Flowers M.E., Logan A.C., Nakamura R., Blazar B.R., et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130:2243–2250. doi: 10.1182/blood-2017-07-793786. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources