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The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation
Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) and TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, TNFR1 and TNFR2 work antithetically to balance immune resp...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294390/ https://www.ncbi.nlm.nih.gov/pubmed/34305946 http://dx.doi.org/10.3389/fimmu.2021.705485 |
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author | Richter, Fabian Williams, Sarah K. John, Katharina Huber, Carina Vaslin, Camille Zanker, Henri Fairless, Richard Pichi, Kira Marhenke, Silke Vogel, Arndt Dhaen, Marie-Ann Herrmann, Stefanie Herrmann, Andreas Pfizenmaier, Klaus Bantel, Heike Diem, Ricarda Kontermann, Roland E. Fischer, Roman |
author_facet | Richter, Fabian Williams, Sarah K. John, Katharina Huber, Carina Vaslin, Camille Zanker, Henri Fairless, Richard Pichi, Kira Marhenke, Silke Vogel, Arndt Dhaen, Marie-Ann Herrmann, Stefanie Herrmann, Andreas Pfizenmaier, Klaus Bantel, Heike Diem, Ricarda Kontermann, Roland E. Fischer, Roman |
author_sort | Richter, Fabian |
collection | PubMed |
description | Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) and TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, TNFR1 and TNFR2 work antithetically to balance immune responses involved in inflammatory diseases. In particular, TNFR1 promotes inflammation and tissue degeneration, whereas TNFR2 contributes to immune modulation and tissue regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative Atrosimab to selectively block TNFR1 signaling, while leaving TNFR2 signaling unaffected. Here, we describe that Atrosimab is highly stable at different storage temperatures and demonstrate its therapeutic efficacy in mouse models of acute and chronic inflammation, including experimental arthritis, non-alcoholic steatohepatitis (NASH) and experimental autoimmune encephalomyelitis (EAE). Our data support the hypothesis that it is sufficient to block TNFR1 signaling, while leaving immune modulatory and regenerative responses via TNFR2 intact, to induce therapeutic effects. Collectively, we demonstrate the therapeutic potential of the human TNFR1 antagonist Atrosimab for treatment of chronic inflammatory diseases. |
format | Online Article Text |
id | pubmed-8294390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82943902021-07-22 The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation Richter, Fabian Williams, Sarah K. John, Katharina Huber, Carina Vaslin, Camille Zanker, Henri Fairless, Richard Pichi, Kira Marhenke, Silke Vogel, Arndt Dhaen, Marie-Ann Herrmann, Stefanie Herrmann, Andreas Pfizenmaier, Klaus Bantel, Heike Diem, Ricarda Kontermann, Roland E. Fischer, Roman Front Immunol Immunology Therapeutics that block tumor necrosis factor (TNF), and thus activation of TNF receptor 1 (TNFR1) and TNFR2, are clinically used to treat inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease and psoriasis. However, TNFR1 and TNFR2 work antithetically to balance immune responses involved in inflammatory diseases. In particular, TNFR1 promotes inflammation and tissue degeneration, whereas TNFR2 contributes to immune modulation and tissue regeneration. We, therefore, have developed the monovalent antagonistic anti-TNFR1 antibody derivative Atrosimab to selectively block TNFR1 signaling, while leaving TNFR2 signaling unaffected. Here, we describe that Atrosimab is highly stable at different storage temperatures and demonstrate its therapeutic efficacy in mouse models of acute and chronic inflammation, including experimental arthritis, non-alcoholic steatohepatitis (NASH) and experimental autoimmune encephalomyelitis (EAE). Our data support the hypothesis that it is sufficient to block TNFR1 signaling, while leaving immune modulatory and regenerative responses via TNFR2 intact, to induce therapeutic effects. Collectively, we demonstrate the therapeutic potential of the human TNFR1 antagonist Atrosimab for treatment of chronic inflammatory diseases. Frontiers Media S.A. 2021-07-07 /pmc/articles/PMC8294390/ /pubmed/34305946 http://dx.doi.org/10.3389/fimmu.2021.705485 Text en Copyright © 2021 Richter, Williams, John, Huber, Vaslin, Zanker, Fairless, Pichi, Marhenke, Vogel, Dhaen, Herrmann, Herrmann, Pfizenmaier, Bantel, Diem, Kontermann and Fischer 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 Richter, Fabian Williams, Sarah K. John, Katharina Huber, Carina Vaslin, Camille Zanker, Henri Fairless, Richard Pichi, Kira Marhenke, Silke Vogel, Arndt Dhaen, Marie-Ann Herrmann, Stefanie Herrmann, Andreas Pfizenmaier, Klaus Bantel, Heike Diem, Ricarda Kontermann, Roland E. Fischer, Roman The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title | The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title_full | The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title_fullStr | The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title_full_unstemmed | The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title_short | The TNFR1 Antagonist Atrosimab Is Therapeutic in Mouse Models of Acute and Chronic Inflammation |
title_sort | tnfr1 antagonist atrosimab is therapeutic in mouse models of acute and chronic inflammation |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294390/ https://www.ncbi.nlm.nih.gov/pubmed/34305946 http://dx.doi.org/10.3389/fimmu.2021.705485 |
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