Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody FD006 in corneal neovascularization.
Pharmacological characteristics and efficacy of a novel anti-angiogenic antibody FD006 in corneal neovascularization.
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新型抗血管生成抗体FD006在角膜新生血管中的药理特征及疗效
DOI：
10.1186/1472-6750-14-17
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发表时间：
2014-02-27
影响因子：
3.5
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Wang Q;Yang J;Tang K;Luo L;Wang L;Tian L;Jiang Y;Feng J;Li Y;Shen B;Lv M;Huang Y
背景血管内皮生长因子（VEGF）是一种重要的血管生成因子.它在生理性和病理性血管生成中起重要作用，并增加血管的渗透性。利用噬菌体抗体展示技术，我们获得了一种新的抗VEGFA IgG，命名为FD 006。本研究评价了FD 006的药理学特性及其对角膜新生血管（Corneal neovascularization，CoNV）的作用。实验分析表明，FD 006的结合能力似乎略强于贝伐珠单抗，ELISA分析的FD 006结合VEGF的EC 50约为0.037 μg/mL，而贝伐珠单抗为0.18 μg/mL。结合动力学实验结果显示，由于FD 006解离速率较慢，FD 006与VEGF结合的亲和力比贝伐珠单抗高2倍;同时，FD 006抑制VEGF诱导的HUVEC增殖的IC 50值为0.031 ± 0.0064 μg/ml，与贝伐珠单抗（0.047 ± 0.0081 μg/ml）相似或略好。与NS相比，结膜下给予FD 006、贝伐珠单抗或地塞米松可显着抑制CoNV的生长（p < 0.01）。在早期阶段，FD 006对CoNV的生长的抑制作用优于贝伐单抗（p < 0.05）。Western blot分析显示，FD 006可抑制VEGF、VEGFR-1、VEGFR-2、MMP-9和ICAM-1的表达，说明其具有良好的抗血管生成活性。
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.
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