New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions
Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe...
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doaj-a97da314f5c448988d3b4dcaf91a01d52020-11-25T03:53:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.578314578314New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future DirectionsNathaniel Edward Bennett Saidu0Nathaniel Edward Bennett Saidu1Chiara Bonini2Anne Dickinson3Magdalena Grce4Marit Inngjerdingen5Ulrike Koehl6Antoine Toubert7Antoine Toubert8Robert Zeiser9Sara Galimberti10Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, CroatiaDepartment of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, NorwayExperimental Hematology Unit, San Raffaele Scientific Institute, Milano, ItalyHaematological Sciences, Newcastle University, Newcastle upon Tyne, United KingdomDivision of Molecular Medicine, Ruđer Bošković Institute, Zagreb, CroatiaDepartment of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, NorwayFaculty of Medicine, Institute of Clinical Immunology, University Leipzig and Fraunhofer IZI, Leipzig, GermanyUniversité de Paris, Institut de Recherche Saint Louis, EMiLy, Inserm U1160, Paris, FranceLaboratoire d'Immunologie et d`Histocompatibilité, AP-HP, Hopital Saint-Louis, Paris, FranceDepartment of Hematology, Oncology and Stem Cell Transplantation, Freiburg University Medical Center, Faculty of Medicine, Freiburg, GermanyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyChronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapies with particular emphasis on tyrosine kinase inhibitors (TKIs). TKIs are a class of compounds that inhibits tyrosine kinases, thereby preventing the dissemination of growth signals and activation of key cellular proteins that are involved in cell growth and division. Because they have been shown to inhibit key kinases in both B cells and T cells that are involved in the pathophysiology of cGvHD, TKIs present new promising therapeutic approaches. Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy. Also, Janus Associated Kinases (JAK1 and JAK2) inhibitors, such as itacitinib (JAK1) and ruxolitinib (JAK1 and 2), are promising in the treatment of cGvHD. Herein, we present the current status and future directions of the use of these new drugs with particular spotlight on their targeting of specific intracellular signal transduction cascades important for cGvHD, in order to shed some light on their possible mode of actions.https://www.frontiersin.org/article/10.3389/fimmu.2020.578314/fullchronic graft-versus-host diseasetyrosine kinase inhibitorsimmunotherapyJanus kinase 1/2hematopoietic stem cell transplantation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nathaniel Edward Bennett Saidu Nathaniel Edward Bennett Saidu Chiara Bonini Anne Dickinson Magdalena Grce Marit Inngjerdingen Ulrike Koehl Antoine Toubert Antoine Toubert Robert Zeiser Sara Galimberti |
spellingShingle |
Nathaniel Edward Bennett Saidu Nathaniel Edward Bennett Saidu Chiara Bonini Anne Dickinson Magdalena Grce Marit Inngjerdingen Ulrike Koehl Antoine Toubert Antoine Toubert Robert Zeiser Sara Galimberti New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions Frontiers in Immunology chronic graft-versus-host disease tyrosine kinase inhibitors immunotherapy Janus kinase 1/2 hematopoietic stem cell transplantation |
author_facet |
Nathaniel Edward Bennett Saidu Nathaniel Edward Bennett Saidu Chiara Bonini Anne Dickinson Magdalena Grce Marit Inngjerdingen Ulrike Koehl Antoine Toubert Antoine Toubert Robert Zeiser Sara Galimberti |
author_sort |
Nathaniel Edward Bennett Saidu |
title |
New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions |
title_short |
New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions |
title_full |
New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions |
title_fullStr |
New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions |
title_full_unstemmed |
New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions |
title_sort |
new approaches for the treatment of chronic graft-versus-host disease: current status and future directions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-10-01 |
description |
Chronic graft-versus-host disease (cGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation that affects various organs leading to a reduced quality of life. The condition often requires enduring immunosuppressive therapy, which can also lead to the development of severe side effects. Several approaches including small molecule inhibitors, antibodies, cytokines, and cellular therapies are now being developed for the treatment of cGvHD, and some of these therapies have been or are currently tested in clinical trials. In this review, we discuss these emerging therapies with particular emphasis on tyrosine kinase inhibitors (TKIs). TKIs are a class of compounds that inhibits tyrosine kinases, thereby preventing the dissemination of growth signals and activation of key cellular proteins that are involved in cell growth and division. Because they have been shown to inhibit key kinases in both B cells and T cells that are involved in the pathophysiology of cGvHD, TKIs present new promising therapeutic approaches. Ibrutinib, a Bruton tyrosine kinase (Btk) inhibitor, has recently been approved by the Food and Drug Administration (FDA) in the United States for the treatment of adult patients with cGvHD after failure of first-line of systemic therapy. Also, Janus Associated Kinases (JAK1 and JAK2) inhibitors, such as itacitinib (JAK1) and ruxolitinib (JAK1 and 2), are promising in the treatment of cGvHD. Herein, we present the current status and future directions of the use of these new drugs with particular spotlight on their targeting of specific intracellular signal transduction cascades important for cGvHD, in order to shed some light on their possible mode of actions. |
topic |
chronic graft-versus-host disease tyrosine kinase inhibitors immunotherapy Janus kinase 1/2 hematopoietic stem cell transplantation |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.578314/full |
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