Efficacy of a recombinant single-chain fragment variable region, VasSF, as a new drug for vasculitis
Authors Kameoka Y, Kishi F, Koura M, Yamakawa Y, Nagasawa R, Ito F, Matsuda J, Suzuki O, Nakayama T, Suzuki K
Received 25 September 2018
Accepted for publication 7 December 2018
Published 5 February 2019 Volume 2019:13 Pages 555—568
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 2
Editor who approved publication: Dr Georgios D. Panos
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
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