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Open Access Research article

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

Qun Wang1, Jing Yang2, Kun Tang3, Longlong Luo2, Liqiang Wang1, Lei Tian1, Yanming Jiang4, Jiannan Feng2, Yan Li2, Beifen Shen2, Ming Lv2* and Yifei Huang1*

Author Affiliations

1 Department of Ophthalmology, General Hospital of People’s Liberation Army, No.28 Fuxing Road, Haidian District, Beijing 100853, China

2 Institute of Basic Medical Sciences, Taiping Road, P.O. Box 130 (3), Beijing 100850, China

3 Department of Ophthalmology, Aerospace center Hospital, No. 15 Yuquan Road, Haidian District, Beijing 100049, China

4 Department of Ophthalmology, The second Artillery General Hospital, No.16 Xinwai Road, Xicheng District, Beijing 100088, China

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BMC Biotechnology 2014, 14:17  doi:10.1186/1472-6750-14-17

Published: 27 February 2014

Abstract

Background

Vascular 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.

Results

FD006 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.

Conclusions

The pharmacological characteristics of FD006 were similar or even a little better than bevacizumab in inhibiting corneal neovascularization.

Keywords:
Neovascularization; Cornea; Bevacizumab; Angiogenesis; Anti-angiogenic treatment