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Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis
- Source :
- Drug Design, Development and Therapy, Vol Volume 13, Pp 555-568 (2019)
- Publication Year :
- 2019
- Publisher :
- Dove Medical Press, 2019.
-
Abstract
- Yosuke Kameoka,1 Fukuko Kishi,1 Minako Koura,2 Yoshio Yamakawa,1 Rora Nagasawa,1 Fuyu Ito,3 Junichiro Matsuda,2 Osamu Suzuki,2 Toshinori Nakayama,4 Kazuo Suzuki1,3–5 1Department of Research and Development, A-CLIP Institute, Ltd., Chiba, Japan; 2Laboratory of Animal Models for Human Diseases, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, Japan; 3Asia International Institute of Infectious Disease Control, Teikyo University, Tokyo, Japan; 4Department of Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan; 5Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan Background: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a pauci-immune disease with the inflammation of the small blood vessels. The efficacies of antibody drugs for induction therapies of vasculitis vary among cases. Here, we developed a novel clone of a single chain Fv region (ScFv) with vasculitis-specific therapeutic potential.Materials and methods: The clone, termed VasSF, was selected from our Escherichia coli expression library of recombinant human ScFv based on the therapeutic efficacy in an SCG/Kj mouse model of MPO-ANCA-associated vasculitis (MAAV), such as improvement of the urinary score and decreased crescent formation in glomeruli, granulomatous in lung, MPO-ANCA biomarkers, the anti-moesin antibody, and some cytokine levels.Results: We identified vasculitis-associated apolipoprotein A-II (VAP2) as a target molecule of the clone and confirmed the independently-established VAP2 antibodies were also therapeutic in SCG/Kj mice. In MAAV, MPO-ANCA and cytokines stimulate neutrophils by facilitating heterodimer formation of VAP2 with apolipoprotein A-I in HDL. Conclusion: VasSF would constitute a novel antibody drug for vasculitis by suppressing the heterodimer formation of the apolipoproteins. Keywords: VasSF, ANCA antibody drug, apolipoprotein, HDL, myeloperoxidase, MPO, SCG/Kj, vasculitis
Details
- Language :
- English
- ISSN :
- 11778881
- Volume :
- ume 13
- Database :
- Directory of Open Access Journals
- Journal :
- Drug Design, Development and Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.905bfd9ef7b4449684e0bc32ec06e3a5
- Document Type :
- article