Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies via the donor immune system driven graft-versus-leukemia effect. However, the therapy is mainly limited by severe acute and chronic graft-versus-host...

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Autores principales:	Lukas M. Braun, Robert Zeiser
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	GvHD stem cell transplant (SCT) kinases ruxolitinib JAK1 and JAK2 inhibitors BTK - Bruton’s tyrosine kinase Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/8e05d6cf6e4145bcafbadad76c11be1c
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spelling	oai:doaj.org-article:8e05d6cf6e4145bcafbadad76c11be1c2021-11-17T06:42:31ZKinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease1664-322410.3389/fimmu.2021.760199https://doaj.org/article/8e05d6cf6e4145bcafbadad76c11be1c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.760199/fullhttps://doaj.org/toc/1664-3224Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies via the donor immune system driven graft-versus-leukemia effect. However, the therapy is mainly limited by severe acute and chronic graft-versus-host disease (GvHD), both being life-threatening complications after allo-HCT. GvHD develops when donor T cells do not only recognize remaining tumor cells as foreign, but also the recipient’s tissue, leading to a severe inflammatory disease. Typical GvHD target organs include the skin, liver and intestinal tract. Currently all approved strategies for GvHD treatment are immunosuppressive therapies, with the first-line therapy being glucocorticoids. However, therapeutic options for glucocorticoid-refractory patients are still limited. Novel therapeutic approaches, which reduce GvHD severity while preserving GvL activity, are urgently needed. Targeting kinase activity with small molecule inhibitors has shown promising results in preclinical animal models and clinical trials. Well-studied kinase targets in GvHD include Rho-associated coiled-coil-containing kinase 2 (ROCK2), spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) to control B- and T-cell activation in acute and chronic GvHD. Janus Kinase 1 (JAK1) and 2 (JAK2) are among the most intensively studied kinases in GvHD due to their importance in cytokine production and inflammatory cell activation and migration. Here, we discuss the role of kinase inhibition as novel treatment strategies for acute and chronic GvHD after allo-HCT.Lukas M. BraunLukas M. BraunRobert ZeiserRobert ZeiserRobert ZeiserRobert ZeiserFrontiers Media S.A.articleGvHDstem cell transplant (SCT)kinasesruxolitinibJAK1 and JAK2 inhibitorsBTK - Bruton’s tyrosine kinaseImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GvHD stem cell transplant (SCT) kinases ruxolitinib JAK1 and JAK2 inhibitors BTK - Bruton’s tyrosine kinase Immunologic diseases. Allergy RC581-607
spellingShingle	GvHD stem cell transplant (SCT) kinases ruxolitinib JAK1 and JAK2 inhibitors BTK - Bruton’s tyrosine kinase Immunologic diseases. Allergy RC581-607 Lukas M. Braun Lukas M. Braun Robert Zeiser Robert Zeiser Robert Zeiser Robert Zeiser Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
description	Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potentially curative therapy for patients suffering from hematological malignancies via the donor immune system driven graft-versus-leukemia effect. However, the therapy is mainly limited by severe acute and chronic graft-versus-host disease (GvHD), both being life-threatening complications after allo-HCT. GvHD develops when donor T cells do not only recognize remaining tumor cells as foreign, but also the recipient’s tissue, leading to a severe inflammatory disease. Typical GvHD target organs include the skin, liver and intestinal tract. Currently all approved strategies for GvHD treatment are immunosuppressive therapies, with the first-line therapy being glucocorticoids. However, therapeutic options for glucocorticoid-refractory patients are still limited. Novel therapeutic approaches, which reduce GvHD severity while preserving GvL activity, are urgently needed. Targeting kinase activity with small molecule inhibitors has shown promising results in preclinical animal models and clinical trials. Well-studied kinase targets in GvHD include Rho-associated coiled-coil-containing kinase 2 (ROCK2), spleen tyrosine kinase (SYK), Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible T-cell kinase (ITK) to control B- and T-cell activation in acute and chronic GvHD. Janus Kinase 1 (JAK1) and 2 (JAK2) are among the most intensively studied kinases in GvHD due to their importance in cytokine production and inflammatory cell activation and migration. Here, we discuss the role of kinase inhibition as novel treatment strategies for acute and chronic GvHD after allo-HCT.
format	article
author	Lukas M. Braun Lukas M. Braun Robert Zeiser Robert Zeiser Robert Zeiser Robert Zeiser
author_facet	Lukas M. Braun Lukas M. Braun Robert Zeiser Robert Zeiser Robert Zeiser Robert Zeiser
author_sort	Lukas M. Braun
title	Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
title_short	Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
title_full	Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
title_fullStr	Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
title_full_unstemmed	Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease
title_sort	kinase inhibition as treatment for acute and chronic graft-versus-host disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/8e05d6cf6e4145bcafbadad76c11be1c
work_keys_str_mv	AT lukasmbraun kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease AT lukasmbraun kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease AT robertzeiser kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease AT robertzeiser kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease AT robertzeiser kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease AT robertzeiser kinaseinhibitionastreatmentforacuteandchronicgraftversushostdisease
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Kinase Inhibition as Treatment for Acute and Chronic Graft-Versus-Host Disease

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