Potent anti-angiogenesis and anti-tumor activity of a novel human anti-VEGF antibody, MIL60
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.
angiogenesis anti-VEGF antibody cancer
Jing Yang Ming Lv Jiannan Feng Qun Wang Chunxia Qiao Zhou Lin Xinying Li Yifei Huang Tingting Zhou Yan Li Beifen Shen
Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China;Department of Pathogen Laboratory of Immunology, Institute of Basic Medical Sciences, Beijing, China Department of Ophthalmology, General Hospital of People”s Liberation Army, Beijing, China
国内会议
苏州
英文
328-336
2014-10-26（万方平台首次上网日期，不代表论文的发表时间）