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The potential for Treg-enhancing therapies in transplantation

Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance against self-antigens, these cells have become a promising tool for the induction of donor-specific tolerance in transplantation medicine. The therapeutic potential of increasing in vivoTreg numbers for a fav...

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Autores principales: Steiner, Romy, Pilat, Nina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019131/
https://www.ncbi.nlm.nih.gov/pubmed/36562079
http://dx.doi.org/10.1093/cei/uxac118
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author Steiner, Romy
Pilat, Nina
author_facet Steiner, Romy
Pilat, Nina
author_sort Steiner, Romy
collection PubMed
description Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance against self-antigens, these cells have become a promising tool for the induction of donor-specific tolerance in transplantation medicine. The therapeutic potential of increasing in vivoTreg numbers for a favorable Treg to Teff cell ratio has already been demonstrated in several sophisticated pre-clinical models and clinical pilot trials. In addition to improving cell quantity, enhancing Treg function utilizing engineering techniques led to encouraging results in models of autoimmunity and transplantation. Here we aim to discuss the most promising approaches for Treg-enhancing therapies, starting with adoptive transfer approaches and ex vivoexpansion cultures (polyclonal vs. antigen specific), followed by selective in vivostimulation methods. Furthermore, we address next generation concepts for Treg function enhancement (CARs, TRUCKs, BARs) as well as the advantages and caveats inherit to each approach. Finally, this review will discuss the clinical experience with Treg therapy in ongoing and already published clinical trials; however, data on long-term results and efficacy are still very limited and many questions that might complicate clinical translation remain open. Here, we discuss the hurdles for clinical translation and elaborate on current Treg-based therapeutic options as well as their potencies for improving long-term graft survival in transplantation.
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spelling pubmed-100191312023-03-17 The potential for Treg-enhancing therapies in transplantation Steiner, Romy Pilat, Nina Clin Exp Immunol Review Series: Therapeutic opportunities for regulatory T cell enhancing approaches (Series Editors: David F. Tough & Giovanna Lombardi) Since the discovery of regulatory T cells (Tregs) as crucial regulators of immune tolerance against self-antigens, these cells have become a promising tool for the induction of donor-specific tolerance in transplantation medicine. The therapeutic potential of increasing in vivoTreg numbers for a favorable Treg to Teff cell ratio has already been demonstrated in several sophisticated pre-clinical models and clinical pilot trials. In addition to improving cell quantity, enhancing Treg function utilizing engineering techniques led to encouraging results in models of autoimmunity and transplantation. Here we aim to discuss the most promising approaches for Treg-enhancing therapies, starting with adoptive transfer approaches and ex vivoexpansion cultures (polyclonal vs. antigen specific), followed by selective in vivostimulation methods. Furthermore, we address next generation concepts for Treg function enhancement (CARs, TRUCKs, BARs) as well as the advantages and caveats inherit to each approach. Finally, this review will discuss the clinical experience with Treg therapy in ongoing and already published clinical trials; however, data on long-term results and efficacy are still very limited and many questions that might complicate clinical translation remain open. Here, we discuss the hurdles for clinical translation and elaborate on current Treg-based therapeutic options as well as their potencies for improving long-term graft survival in transplantation. Oxford University Press 2022-12-23 /pmc/articles/PMC10019131/ /pubmed/36562079 http://dx.doi.org/10.1093/cei/uxac118 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Immunology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Series: Therapeutic opportunities for regulatory T cell enhancing approaches (Series Editors: David F. Tough & Giovanna Lombardi)
Steiner, Romy
Pilat, Nina
The potential for Treg-enhancing therapies in transplantation
title The potential for Treg-enhancing therapies in transplantation
title_full The potential for Treg-enhancing therapies in transplantation
title_fullStr The potential for Treg-enhancing therapies in transplantation
title_full_unstemmed The potential for Treg-enhancing therapies in transplantation
title_short The potential for Treg-enhancing therapies in transplantation
title_sort potential for treg-enhancing therapies in transplantation
topic Review Series: Therapeutic opportunities for regulatory T cell enhancing approaches (Series Editors: David F. Tough & Giovanna Lombardi)
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10019131/
https://www.ncbi.nlm.nih.gov/pubmed/36562079
http://dx.doi.org/10.1093/cei/uxac118
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