Eras of designer Tregs: Harnessing synthetic biology for immune suppression

Karoliina Tuomela; Kevin Salim; Megan K. Levings

doi:10.1111/imr.13254

journal article Open Access Jul 31, 2023

Eras of designer Tregs: Harnessing synthetic biology for immune suppression

Karoliina Tuomela Kevin Salim Megan K. Levings

Immunological Reviews Vol. 320 No. 1 pp. 250-267 · Wiley

View at Publisher Save 10.1111/imr.13254

Abstract

SummarySince their discovery, CD4+CD25hiFOXP3hi regulatory T cells (Tregs) have been firmly established as a critical cell type for regulating immune homeostasis through a plethora of mechanisms. Due to their immunoregulatory power, delivery of polyclonal Tregs has been explored as a therapy to dampen inflammation in the settings of transplantation and autoimmunity. Evidence shows that Treg therapy is safe and well‐tolerated, but efficacy remains undefined and could be limited by poor persistence in vivo and lack of antigen specificity. With the advent of new genetic engineering tools, it is now possible to create bespoke “designer” Tregs that not only overcome possible limitations of polyclonal Tregs but also introduce new features. Here, we review the development of designer Tregs through the perspective of three ‘eras’: (1) the era of FOXP3 engineering, in which breakthroughs in the biological understanding of this transcription factor enabled the conversion of conventional T cells to Tregs; (2) the antigen‐specificity era, in which transgenic T‐cell receptors and chimeric antigen receptors were introduced to create more potent and directed Treg therapies; and (3) the current era, which is harnessing advanced genome‐editing techniques to introduce and refine existing and new engineering approaches. The year 2022 marked the entry of “designer” Tregs into the clinic, with exciting potential for application and efficacy in a wide variety of immune‐mediated diseases.

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Details

Published: Jul 31, 2023
Vol/Issue: 320(1)
Pages: 250-267
License: View

Authors

K

Karoliina Tuomela

BC Children's Hospital Research Institute Vancouver British Columbia Canada; Department of Surgery University of British Columbia Vancouver British Columbia Canada

K

Kevin Salim

BC Children's Hospital Research Institute Vancouver British Columbia Canada; Department of Surgery University of British Columbia Vancouver British Columbia Canada

M

Megan K. Levings

BC Children's Hospital Research Institute Vancouver British Columbia Canada; Department of Surgery University of British Columbia Vancouver British Columbia Canada; School of Biomedical Engineering University of British Columbia Vancouver British Columbia Canada

Funding

Canadian Institutes of Health Research Award: FDN‐154304

Cite This Article

Karoliina Tuomela, Kevin Salim, Megan K. Levings (2023). Eras of designer Tregs: Harnessing synthetic biology for immune suppression. Immunological Reviews, 320(1), 250-267. https://doi.org/10.1111/imr.13254

Eras of designer Tregs: Harnessing synthetic biology for immune suppression

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