TY - JOUR
T1 - New Approaches for the Treatment of Chronic Graft-Versus-Host Disease
T2 - Current Status and Future Directions
AU - Saidu, Nathaniel Edward Bennett
AU - Bonini, Chiara
AU - Dickinson, Anne
AU - Grce, Magdalena
AU - Inngjerdingen, Marit
AU - Koehl, Ulrike
AU - Toubert, Antoine
AU - Zeiser, Robert
AU - Galimberti, Sara
N1 - Funding Information:
This work was supported by COST (European Cooperation in Science and Technology), www.cost.eu—CA17138 EUROGRAFT. AT was supported by the French Government’s Investissement d’Avenir Program, Laboratoire d’Excellence “Milieu Intérieur” Grant ANR-10-LABX-69-01 and by the by the Agence Nationale de la Recherche (Project RANKLthym ANR-19-CE18-0021-02).
Publisher Copyright:
© Copyright © 2020 Saidu, Bonini, Dickinson, Grce, Inngjerdingen, Koehl, Toubert, Zeiser and Galimberti.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10/9
Y1 - 2020/10/9
N2 - 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.
AB - 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.
KW - chronic graft-versus-host disease
KW - hematopoietic stem cell transplantation
KW - immunotherapy
KW - Janus kinase 1/2
KW - tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=85094125320&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85094125320&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.578314
DO - 10.3389/fimmu.2020.578314
M3 - Review article
C2 - 33162993
AN - SCOPUS:85094125320
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
M1 - 578314
ER -