Regulatory T cell therapy of graft-versus-host disease: Advances and challenges

Mehrdad Hefazi; Sara Bolivar-Wagers; Bruce R. Blazar

doi:10.3390/ijms22189676

Regulatory T cell therapy of graft-versus-host disease: Advances and challenges

Mehrdad Hefazi, Sara Bolivar-Wagers, Bruce R. Blazar

Research output: Contribution to journal › Review article › peer-review

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.

Original language	English (US)
Article number	9676
Journal	International journal of molecular sciences
Volume	22
Issue number	18
DOIs	https://doi.org/10.3390/ijms22189676
State	Published - Sep 2021

Bibliographical note

Funding Information:
Conflicts of Interest: B.R.B. serves on advisory boards for Magenta Therapeutics and BlueRock Theapeutics; receives research funding from BlueRock Therapeutics, Rheos Medicines, Equilibre Pharmaceuticals Corp., and Carisma Therapeutics, Inc; is a co-founder of Tmunity Therapeutics; and receives the following NIH grant support: R37 AI34495, R01 HL147324, R01 HL155114, and R01 HL56067.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Allogeneic hematopoietic stem cell transplantation
GVHD
Graft-versus-host disease
Regulatory T cells
Treg

PubMed: MeSH publication types

Journal Article
Review

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10.3390/ijms22189676

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title = "Regulatory T cell therapy of graft-versus-host disease: Advances and challenges",

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 = "Allogeneic hematopoietic stem cell transplantation, GVHD, Graft-versus-host disease, Regulatory T cells, Treg",

author = "Mehrdad Hefazi and Sara Bolivar-Wagers and Blazar, {Bruce R.}",

note = "Funding Information: Conflicts of Interest: B.R.B. serves on advisory boards for Magenta Therapeutics and BlueRock Theapeutics; receives research funding from BlueRock Therapeutics, Rheos Medicines, Equilibre Pharmaceuticals Corp., and Carisma Therapeutics, Inc; is a co-founder of Tmunity Therapeutics; and receives the following NIH grant support: R37 AI34495, R01 HL147324, R01 HL155114, and R01 HL56067. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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N2 - 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.

AB - 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.

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Regulatory T cell therapy of graft-versus-host disease: Advances and challenges

Abstract

Bibliographical note

Keywords

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