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T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of preference for numerous malignant and non-malignant hemopathies. The outcome of this approach is significantly hampered by not only graft-versus-host disease (GvHD), but also infections and relapses that may occur because...

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Autores principales: Gaudeaux, Pierre, Moirangthem, Ranjita Devi, Bauquet, Aurélie, Simons, Laura, Joshi, Akshay, Cavazzana, Marina, Nègre, Olivier, Soheili, Shabi, André, Isabelle
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300856/
https://www.ncbi.nlm.nih.gov/pubmed/35874778
http://dx.doi.org/10.3389/fimmu.2022.956919
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author Gaudeaux, Pierre
Moirangthem, Ranjita Devi
Bauquet, Aurélie
Simons, Laura
Joshi, Akshay
Cavazzana, Marina
Nègre, Olivier
Soheili, Shabi
André, Isabelle
author_facet Gaudeaux, Pierre
Moirangthem, Ranjita Devi
Bauquet, Aurélie
Simons, Laura
Joshi, Akshay
Cavazzana, Marina
Nègre, Olivier
Soheili, Shabi
André, Isabelle
author_sort Gaudeaux, Pierre
collection PubMed
description Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of preference for numerous malignant and non-malignant hemopathies. The outcome of this approach is significantly hampered by not only graft-versus-host disease (GvHD), but also infections and relapses that may occur because of persistent T-cell immunodeficiency following transplantation. Reconstitution of a functional T-cell repertoire can take more than 1 year. Thus, the major challenge in the management of allogeneic HSCT relies on the possibility of shortening the window of immune deficiency through the acceleration of T-cell recovery, with diverse, self-tolerant, and naïve T cells resulting from de novo thymopoiesis from the donor cells. In this context, adoptive transfer of cell populations that can give rise to mature T cells faster than HSCs while maintaining a safety profile compatible with clinical use is of major interest. In this review, we summarize current advances in the characterization of thymus seeding progenitors, and their ex vivo generated counterparts, T-cell progenitors. Transplantation of the latter has been identified as a worthwhile approach to shorten the period of immune deficiency in patients following allogeneic HSCT, and to fulfill the clinical objective of reducing morbimortality due to infections and relapses. We further discuss current opportunities for T-cell progenitor-based therapy manufacturing, including iPSC cell sources and off-the-shelf strategies. These opportunities will be analyzed in the light of results from ongoing clinical studies involving T-cell progenitors.
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spelling pubmed-93008562022-07-22 T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation Gaudeaux, Pierre Moirangthem, Ranjita Devi Bauquet, Aurélie Simons, Laura Joshi, Akshay Cavazzana, Marina Nègre, Olivier Soheili, Shabi André, Isabelle Front Immunol Immunology Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of preference for numerous malignant and non-malignant hemopathies. The outcome of this approach is significantly hampered by not only graft-versus-host disease (GvHD), but also infections and relapses that may occur because of persistent T-cell immunodeficiency following transplantation. Reconstitution of a functional T-cell repertoire can take more than 1 year. Thus, the major challenge in the management of allogeneic HSCT relies on the possibility of shortening the window of immune deficiency through the acceleration of T-cell recovery, with diverse, self-tolerant, and naïve T cells resulting from de novo thymopoiesis from the donor cells. In this context, adoptive transfer of cell populations that can give rise to mature T cells faster than HSCs while maintaining a safety profile compatible with clinical use is of major interest. In this review, we summarize current advances in the characterization of thymus seeding progenitors, and their ex vivo generated counterparts, T-cell progenitors. Transplantation of the latter has been identified as a worthwhile approach to shorten the period of immune deficiency in patients following allogeneic HSCT, and to fulfill the clinical objective of reducing morbimortality due to infections and relapses. We further discuss current opportunities for T-cell progenitor-based therapy manufacturing, including iPSC cell sources and off-the-shelf strategies. These opportunities will be analyzed in the light of results from ongoing clinical studies involving T-cell progenitors. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9300856/ /pubmed/35874778 http://dx.doi.org/10.3389/fimmu.2022.956919 Text en Copyright © 2022 Gaudeaux, Moirangthem, Bauquet, Simons, Joshi, Cavazzana, Nègre, Soheili and André https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gaudeaux, Pierre
Moirangthem, Ranjita Devi
Bauquet, Aurélie
Simons, Laura
Joshi, Akshay
Cavazzana, Marina
Nègre, Olivier
Soheili, Shabi
André, Isabelle
T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title_full T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title_fullStr T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title_full_unstemmed T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title_short T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation
title_sort t-cell progenitors as a new immunotherapy to bypass hurdles of allogeneic hematopoietic stem cell transplantation
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300856/
https://www.ncbi.nlm.nih.gov/pubmed/35874778
http://dx.doi.org/10.3389/fimmu.2022.956919
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