Ruxolitinib, a JAK1/JAK2 selective inhibitor, ameliorates acute and chronic steroid-refractory GvHD mouse models
Aim: Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation. Material & methods: We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD. Results: Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD. Additionally, we describe a novel humanized GvHD model in which immunodeficient NOG animals are engineered to produce human IL-15 to facilitate enhanced T- and NK cell engraftment, leading to severe GvHD. Conclusion: Ruxolitinib treatment ameliorated disease symptoms resulting from targeted immune modulation via JAK/signal transducers and activators of transcription signaling inhibition.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Immunotherapy - 13(2021), 12 vom: 06. Aug., Seite 977-987 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Huarte, Eduardo [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 01.02.2022 Date Revised 01.02.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.2217/imt-2021-0013 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327315296 |
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| 100 | 1 | |a Huarte, Eduardo |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ruxolitinib, a JAK1/JAK2 selective inhibitor, ameliorates acute and chronic steroid-refractory GvHD mouse models |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Graft-versus-host disease (GvHD) is a major complication arising in patients undergoing allogenic hematopoietic stem cell transplantation. Material & methods: We tested ruxolitinib (a selective JAK1/2 inhibitor) efficacy in three different preclinical models of GvHD. Results: Ruxolitinib, at doses that mimic clinically achievable human JAK/signal transducers and activators of transcription target inhibition, significantly reduced alloreactive T-cell activation and infiltration in the lung and skin, leading to improved outcomes in two experimental models of steroid-refractory acute and chronic GvHD. Additionally, we describe a novel humanized GvHD model in which immunodeficient NOG animals are engineered to produce human IL-15 to facilitate enhanced T- and NK cell engraftment, leading to severe GvHD. Conclusion: Ruxolitinib treatment ameliorated disease symptoms resulting from targeted immune modulation via JAK/signal transducers and activators of transcription signaling inhibition | ||
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| 700 | 1 | |a Juvekar, Ashish |e verfasserin |4 aut | |
| 700 | 1 | |a Dubé, Philip |e verfasserin |4 aut | |
| 700 | 1 | |a Sarah, Sarala |e verfasserin |4 aut | |
| 700 | 1 | |a Stephens, Lynn |e verfasserin |4 aut | |
| 700 | 1 | |a Stewart, Becky |e verfasserin |4 aut | |
| 700 | 1 | |a Long, Brian |e verfasserin |4 aut | |
| 700 | 1 | |a Czerniak, Philip |e verfasserin |4 aut | |
| 700 | 1 | |a Oliver, Julian |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Paul |e verfasserin |4 aut | |
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