Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
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
_version_ 1783725224132345856
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
work_keys_str_mv AT richterfabian thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT williamssarahk thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT johnkatharina thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT hubercarina thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT vaslincamille thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT zankerhenri thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT fairlessrichard thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT pichikira thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT marhenkesilke thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT vogelarndt thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT dhaenmarieann thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT herrmannstefanie thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT herrmannandreas thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT pfizenmaierklaus thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT bantelheike thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT diemricarda thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT kontermannrolande thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT fischerroman thetnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT richterfabian tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT williamssarahk tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT johnkatharina tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT hubercarina tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT vaslincamille tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT zankerhenri tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT fairlessrichard tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT pichikira tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT marhenkesilke tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT vogelarndt tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT dhaenmarieann tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT herrmannstefanie tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT herrmannandreas tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT pfizenmaierklaus tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT bantelheike tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT diemricarda tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT kontermannrolande tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation
AT fischerroman tnfr1antagonistatrosimabistherapeuticinmousemodelsofacuteandchronicinflammation