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Production of VEGF Neutralizing McAb And Its Inhibitory Effect on Lung Cancer
Zhang Lihong1, Liu Xianglei1, Gu Yinfang2, Sun Yunchun2, Chen Xudong3, Cai Maohuai3, Zhang Famin4, Lin Feng2*, Wu Jiong1,2*
1Xinyuan Institute of Medicine and Biotechnology, College of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, China; 2Richard J.Roberts Institute of Biotechnology, Yixing 214200, China; 3Yancheng Second People’s Hospital, Yancheng 22403, China; 4Wuhan Hua Shi Tong Biomedical Science and Technology Limited Company, Wuhan 430074, China
Abstract: Vascular endothelial growth factor (VEGF) is an angiogenesis-inducing factor playing a pivotal role in cancer growth and metastasis， and it has been the main target for developing new drugs to inhibit neoplastic growth or to keep tumor dormancy by blocking the formation and expansion of new capilaries. In this study， we developed a VEGF neutralizing monoclonal antibody (McAb) and investigated its antiangiogenic effect in a lung cancer nude mice model. The VEGF neutralizing McAb was obtained by immunizing Balb/c mice with plasmid DNA encoding VEGF full-length protein， its neutralizing activity was tested by exposing HuVEC to various concentrations of VEGF with or without addition of the VEGF McAb， and VEGFR-2 phosphorylation (activation) status was determined by Western blot. The VEGF McAb could suppress VEGFR-2 tyrosine phosphorylation activated by VEGF. Moreover， its anti-angiogenesis effect was studied using a nude mouse model with A549 lung cancer cell inoculation， 50 μg VEGF McAb treatment led to a 51.5% inhibition ratio of tumor weight and the tumor growth inhibition rate was 62.5%. Together， our results demonstrate that the VEGF neutralizing McAb may not only significantly suppress VEGFR-2 mediated signaling but also inhibit the growth of lung cancer in a mouse model.
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