Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody FD006 in corneal neovascularization

BMC Biotechnology

Research Article

Kun Tang¹  Yifei Huang²  Lei Tian²  Qun Wang²  Liqiang Wang²  Yanming Jiang³  Ming Lv⁴  Beifen Shen⁴  Jing Yang⁴  Jiannan Feng⁴  Yan Li⁴  Longlong Luo⁴ 

[1] Department of Ophthalmology, Aerospace center Hospital, No. 15 Yuquan Road, Haidian District, 100049, Beijing, China;Department of Ophthalmology, General Hospital of People’s Liberation Army, No.28 Fuxing Road, Haidian District, 100853, Beijing, China;Department of Ophthalmology, The second Artillery General Hospital, No.16 Xinwai Road, Xicheng District, 100088, Beijing, China;Institute of Basic Medical Sciences, P.O. Box 130 (3), Taiping Road, 100850, Beijing, China;

关键词: Neovascularization;    Cornea;    Bevacizumab;    Angiogenesis;    Anti-angiogenic treatment;   

DOI  :  10.1186/1472-6750-14-17

 received in 2013-12-16, accepted in 2014-02-24,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundVascular endothelial growth factor (VEGF) is a key angiogenic factors. It plays an important role in both physiologic and pathologic angiogenesis and increases permeability across the vessels. Using antibody phage display technology, we obtained a novel anti-VEGFA IgG, named as FD006. In this study, the pharmacological characteristics and efficacy of FD006 in corneal neovascularization (CoNV) were evaluated.ResultsFD006 was predicted to have similar binding mode to bevacizumab. Experimental analysis showed that the binding ability of FD006 seemed a little stronger than bevacizumab, for the EC50 of FD006 to bind VEGF analyzed by ELISA was about 0.037 μg/mL while that of bevacizumab was 0.18 μg/mL. Binding kinetics assays showed similar results that FD006 possessed 2-fold higher affinity to bind VEGF than bevacizumab due to slower dissociation rate of FD006; meanwhile, FD006 inhibited the VEGF-induced proliferation of HUVEC with an IC50 value of 0.031 ± 0.0064 μg/ml, which seemed similar or a litter better than bevacizumab (0.047 ± 0.0081 μg/ml). The subconjunctival administration of FD006, bevacizumab or dexamethasone could significantly inhibit the growth of CoNV contrasting to N.S (p < 0.01). At the early stage, FD006 showed better inhibitory effect on the growth of CoNV compared with bevacizumab (p < 0.05). Western blot analysis showed that FD006 could inhibit the expression of VEGF, VEGFR-1, VEGFR-2, MMP-9 and ICAM-1, which could explain its favorable anti-angiogenic activity.ConclusionsThe pharmacological characteristics of FD006 were similar or even a little better than bevacizumab in inhibiting corneal neovascularization.

【 授权许可】

Unknown   
© Wang et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.