Interaction between bevacizumab and murine VEGF-A: A reassessment
Interaction between bevacizumab and murine VEGF-A: A reassessment
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DOI：
10.1167/iovs.07-1175
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Ferrara, Napoleone
中科院分区：
文献类型：
--
作者：
Yu, Lanlan;Wu, Xiumin;Ferrara, Napoleone
目的。贝伐单抗是美国食品和药物管理局批准用于癌症治疗的人源化抗人血管内皮生长因子-A单抗，用于治疗新生血管性老年性黄斑变性。早期的研究表明，贝伐单抗具有物种特异性，缺乏中和小鼠(M)血管内皮生长因子-A的能力。然而，最近的一项研究报道，贝伐单抗是一种有效的血管生成和淋巴管生成的抑制剂。作者试图重新评估贝伐单抗与mVEGF-A之间的相互作用。方法作者通过Western印迹分析、Biacore血浆共振和内皮细胞增殖试验来表征贝伐单抗与mVEGF-A之间的相互作用。他们还测试了贝伐单抗在两种体内小鼠模型中是否有任何作用，激光诱导的脉络膜新生血管(CNV)和黑色素瘤生长。结果：Western印迹检测到非常弱的相互作用，但Biacore检测到mVEGF和贝伐单抗之间没有可测量的相互作用。贝伐单抗不能抑制mVEGF刺激的内皮细胞增殖。此外，在CNV和肿瘤模型中，贝伐单抗与对照抗体没有区别，而交叉反应的抗血管内皮生长因子-A单抗具有显著的抑制作用。结论贝伐单抗与mVEGF-A的相互作用极弱，未能导致免疫中和作用，如几种生物检测方法所评估的那样。
PURPOSE. Bevacizumab is a humanized anti-human VEGF-A monoclonal antibody (mAb) approved by the United States Food and Drug Administration for cancer therapy and used off label to treat neovascular age-related macular degeneration. Earlier studies characterized bevacizumab as species specific and lacking the ability to neutralize murine (m) VEGF-A. However, a recent study reported that bevacizumab is a potent inhibitor of hemangiogenesis and lymphangiogenesis in murine models. The authors sought to reassess the interaction between bevacizumab and mVEGF-A.METHODS. The authors performed Western blot analysis, plasmon resonance by BIAcore, and endothelial cell proliferation assays to characterize the interaction between bevacizumab and mVEGF-A. They also tested whether bevacizumab had any effects in two in vivo murine models, laser-induced choroidal neovascularization (CNV) and melanoma growth.RESULTS. Western blot detected a very weak interaction, but BIAcore detected no measurable interaction between mVEGF and bevacizumab. Bevacizumab failed to inhibit mVEGF-stimulated endothelial cell proliferation. In addition, bevacizumab was indistinguishable from the control antibody in the CNV and tumor models, whereas a cross-reactive anti-VEGF-A mAb had dramatic inhibitory effects.CONCLUSIONS. Bevacizumab has an extremely weak interaction with mVEGF-A, which fails to result in immunoneutralization as assessed by several bioassays.