Abstract
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.
Highlights
Vascular endothelial growth factor (VEGF) is a key angiogenic factors
The predicted binding mode of FD006 was similar to bevacizumab Using antibody phage display library, we obtained a novel anti-VEGFA antibody, named as FD006
Using interactive graphics and the hard-sphere approximation for atoms, we found that the FD006 variable region was fitted into the binding site of VEGFA which identified by bevacizumab
Summary
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. There is a dynamic balance between pro- and anti-angiogenic factors in the cornea that plays a key role in maintaining avascularity. Vascular endothelial growth factor (VEGF) plays an important role in both physiologic and pathologic angiogenesis and increases permeability across the vessels. There are many VEGF inhibitors which are in advanced clinical use for ocular neovascularization, such as Lucentis, Macugen and bevacizumab/Avastin Administration of these drugs in CoNv has been associated with promising results [13,14,15]
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