The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis
AbstractCurrent 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. View Full-Text
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Huang, R.; Li, J.; Wang, Y.; Zhang, L.; Ma, X.; Wang, H.; Li, W.; Cao, X.; Xu, H.; Hu, J. The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis. Int. J. Mol. Sci. 2018, 19, 2683.
Huang R, Li J, Wang Y, Zhang L, Ma X, Wang H, Li W, Cao X, Xu H, Hu J. The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis. International Journal of Molecular Sciences. 2018; 19(9):2683.Chicago/Turabian Style
Huang, Ruijing; Li, Jian; Wang, Yibo; Zhang, Lihua; Ma, Xiaohui; Wang, Hongyu; Li, Wenlei; Cao, Xiaodan; Xu, Hanmei; Hu, Jialiang. 2018. "The Protective Effect of a Long-Acting and Multi-Target HM-3-Fc Fusion Protein in Rheumatoid Arthritis." Int. J. Mol. Sci. 19, no. 9: 2683.
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