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The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis
Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the i...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163367/ https://www.ncbi.nlm.nih.gov/pubmed/30201867 http://dx.doi.org/10.3390/ijms19092683 |
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author | Huang, Ruijing Li, Jian Wang, Yibo Zhang, Lihua Ma, Xiaohui Wang, Hongyu Li, Wenlei Cao, Xiaodan Xu, Hanmei Hu, Jialiang |
author_facet | Huang, Ruijing Li, Jian Wang, Yibo Zhang, Lihua Ma, Xiaohui Wang, Hongyu Li, Wenlei Cao, Xiaodan Xu, Hanmei Hu, Jialiang |
author_sort | Huang, Ruijing |
collection | PubMed |
description | Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment. |
format | Online Article Text |
id | pubmed-6163367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61633672018-10-10 The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis Huang, Ruijing Li, Jian Wang, Yibo Zhang, Lihua Ma, Xiaohui Wang, Hongyu Li, Wenlei Cao, Xiaodan Xu, Hanmei Hu, Jialiang Int J Mol Sci Article Current treatment of rheumatoid arthritis (RA) is limited by relative shortage of treatment targets. HM-3 is a novel anti-RA polypeptide consisting of 18 amino acids with integrin αVβ3 and α5β1 as targets. Previous studies confirmed that HM-3 effectively inhibited the synovial angiogenesis and the inflammatory response. However, due to its short half-life, the anti-RA activity was achieved by frequent administration. To extend the half-life of HM-3, we designed a fusion protein with name HM-3-Fc, by combination of modified Fc segment of immunoglobulin 4 (IgG4) with HM-3 polypeptide. In vitro cell experiments demonstrated that HM-3-Fc inhibited the proliferation of splenic lymphocytes and reduced the release of TNF-α from macrophages. The pharmacodynamics studies on mice paw in Collagen-Induced Arthritis (CIA) model demonstrated that HM-3-Fc administered once in 5 days in the 50 and 25 mg/kg groups, or once in 7 days in the 25 mg/kg group showed a better protective effect within two weeks than the positive control adalimumab and HM-3 group. Preliminary pharmacokinetic studies in cynomolgus confirmed that the in vivo half-life of HM-3-Fc was 15.24 h in comparison with 1.32 min that of HM-3, which demonstrated that an Fc fusion can effectively increase the half-life of HM-3 and make it possible for further reduction of subcutaneous injection frequency. Fc-HM-3 is a long-acting active molecule for RA treatment. MDPI 2018-09-10 /pmc/articles/PMC6163367/ /pubmed/30201867 http://dx.doi.org/10.3390/ijms19092683 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Huang, Ruijing Li, Jian Wang, Yibo Zhang, Lihua Ma, Xiaohui Wang, Hongyu Li, Wenlei Cao, Xiaodan Xu, Hanmei Hu, Jialiang The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title | The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title_full | The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title_fullStr | The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title_full_unstemmed | The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title_short | The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis |
title_sort | protective effect of a long-acting and multi-target hm-3-fc fusion protein in rheumatoid arthritis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6163367/ https://www.ncbi.nlm.nih.gov/pubmed/30201867 http://dx.doi.org/10.3390/ijms19092683 |
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