Anti-complement component 5 antibody targeting MG4 domain inhibits choroidal neovascularization
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Dong Hyun Jo1,2, Jin Hyoung Kim1, Wonjun Yang3,4,5, Hyori Kim6, Shinjae Chang7, Dongjo Kim7, Minseok Chang7, Kihwang Lee8, Junho Chung3,4,5 and Jeong Hun Kim1,2,9
1Fight Against Angiogenesis-Related Blindness (FARB) Laboratory, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
2Department of Biomedical Sciences and Protein Metabolism, Medical Research Center, Seoul National University College of Medicine, Seoul, Republic of Korea
3Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea
4Department of Cancer Biology, Seoul National University College of Medicine, Seoul, Republic of Korea
5Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
6Asan Institute for Life Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
7Biotechnology Research Institute, Celltrion, Inc., Incheon, Republic of Korea
8Department of Ophthalmology, Ajou University School of Medicine, Suwon, Republic of Korea
9Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea
Junho Chung, email: [email protected]
Jeong Hun Kim, email: [email protected]
Keywords: age-related macular degeneration, choroidal neovascularization, complement component 5, MG4 domain, therapeutic antibody
Received: January 31, 2017 Accepted: March 15, 2017 Published: April 19, 2017
Age-related macular degeneration (AMD) is one of the main causes of visual impairment in adults. Visual deterioration is more prominent in neovascular AMD with choroidal neovascularization (CNV). Clinical and postmortem studies suggested that complement system activation might induce CNV. In this study, we demonstrated that an anti-mouse complement component 5 (C5) antibody targeting MG4 domain of β chain effectively inhibited CNV which was induced by laser photocoagulation in mice. The targeted epitope of this anti-C5 antibody was different from that of currently utilized anti-C5 antibody (eculizumab) in the MG7 domain in which a single nucleotide polymorphism (R885H/C) results in poor response to eculizumab. Even with targeting MG4 domain, this anti-C5 antibody reduced production of C5a, monocyte chemoattractant protein-1 and vascular endothelial growth factor to prevent infiltration of F4/80-positive cells into CNV lesions and formation of CNV. Furthermore, anti-C5 antibody targeting MG4 domain induced no definite toxicity in normal retina. These results demonstrated that anti-C5 antibody targeting MG4 domain inhibited CNV in neovascular AMD.
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