Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis
| Autor: | Yosuke, Kameoka, Fukuko, Kishi, Minako, Koura, Yoshio, Yamakawa, Rora, Nagasawa, Fuyu, Ito, Junichiro, Matsuda, Osamu, Suzuki, Toshinori, Nakayama, Kazuo, Suzuki |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Drug Design
Development and Therapy Dose-Response Relationship Drug HDL VasSF apolipoprotein MPO Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis SCG/Kj Recombinant Proteins vasculitis Mice Inbred C57BL Mice myeloperoxidase Peptide Library Animals Humans Corrigendum ANCA antibody drug Single-Chain Antibodies Original Research |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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