Anti-angiogenesis and anti-tumor activity of the fully human anti-VEGF165 monoclonal antibody obtained from the five-feature transgenic mice

This study was focus on the anti-angiogenesis and anti-tumor activity both in vitro and in vivo of novel fully human anti-VEGF165 monoclonal antibody obtained from five-feature transgenic mice.The effect of human anti-VEGF mAb on migration of vascular endothelial cells was observed by scratch assay;inhibitory effect of human anti-VEGF mAb on VEGF-secreting cells was determined by MTT assay and followed by Annexin V/PI double-staining assay to detect apoptosis induced by the mAb;orthotopic gastric tumor model was established to determine anti-angiogenesis and anti-tumor activity in vivo.Our novel human anti-VEGF mAb was found dramatically inhibit HUVEC cells migration and proliferation at dose 120 μg/mL in vitro while remarkable inhibition effect on four kinds of VEGF-secreting tumor cells such as HepG2，BGC823，MCF-7，SGC-7901 tested in our study might be due to the apoptosis.After mAb was administrated at dose 10 mg/kg and 5 mg/kg for 40 days tumor inhibition was calculated as 49.9% and 27.7% respectively.And immunohistochemistry analysis of orthotopic gastric tumors confirmed significant inhibition of tumor VEGF expression and neovascularization.The fully human anti-VEGF mAb exhibited remarkable anti-angiogenesis and anti-tumor growth effects both in vitro and in vivo and it is feasible to produce therapeutic fully human monoclonal antibodies using five-feature transgenic mice.