【摘 要】
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Angiogenesis is crucial for tumor development, growth and metastasis.Vascular endothelial growth factor (VEGF) has been implicated in promoting sol id tumor growth and metastasis via stimulating tumor
【机 构】
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Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China;Department of Pathogen
【出 处】
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第七届国际分子模拟与信息技术应用学术会议
论文部分内容阅读
Angiogenesis is crucial for tumor development, growth and metastasis.Vascular endothelial growth factor (VEGF) has been implicated in promoting sol id tumor growth and metastasis via stimulating tumor-associated angiogenesis, and blocking the activity of VEG Fcan starve tumors.Avastin, which is a humanized anti-VEG F ant ibody, has been successfully applied in clinics since 2004.However, the price of Avastin is extremely high for Chinese people.Here, we report a novel human anti-VEGF neutralizing antibody, MIL60, which shows an affinity comparable to that of Avastin (the KD value of M IL60 was 44.5 pM, while that of Avastin was 42.7 pM).M I L60 displays favorable actions in inhibiting VEGF-triggered endothelial cell proliferation (the ICso value of MIL60 was 31±6.4 ng/ml and that of Avastin was 47±8.1 ng/ml), migration (8 μg/ml or 0.8 μg/ml MIL60 versusthe control: P＜0.05) and tube formation (2 μg/ml or 0.2 μg/ml MIL60 versusthe control: P＜0.05) viathe VEG FR2 signaling pathway.Moreover, M IL60 was shown to inhibit tumor growth and angiogenesis in vivo in xenograft models of human colon carcinoma and ovarian cancer using immunotherapy and immunohistochemistryanalysis (MIL60 versus N.S.: P=0.0007;Avastin versus N.S.: P=0.00046).These data suggest that M IL60 is a potential therapeutic, anti-angiogenic agent.Our work provides a novel anti-VEG Fantibody, which can be considered an anti-tumor antibody candidate and a new option for patients with various cancers.
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