title: Fully human VEGFR2 monoclonal antibody BC001 attenuates tumor angiogenesis and inhibits tumor growth.
abstract: The critical role of VEGFR2 in tumor neovascularization and progression has allowed the design of clinically beneficial therapies based on it. Here we show that BC001, a new fully human anti-VEGFR2 monoclonal antibody, inhibits VEGF-stimulated endothelial cell migration, tube formation, and effectively suppressed the transdifferentiation of cancer stem cells into endothelial cells in vitro. Since BC001 exhibited no activity against the mouse VEGFR2 and mouse based study was required to confirm its efficacy in vivo, BC101, the mouse analogue of BC001, was developed. BC101 significantly attenuated angiogenesis according to Matrigel plug assay and resulted in ~80% growth inhibition of mouse B16F10 homograft tumors relative to vehicle control. Similarly, human analogue BC001 suppressed the growth of human xenograft tumors HCT116 and BGC823. Furthermore, immunohistochemical results showed reduced expression of CD31, VEGFR2 and Ki-67, as well as increased expression of Caspase 3 in BC001-treated tumor, which indicated BC001 was able to significantly decrease microvessel density, suppress proliferation and promote apoptosis. These results demonstrate the fully human VEGFR2 monoclonal antibody BC001 can work as an effective inhibitor of tumor angiogenesis and tumor growth both in vitro and in vivo.
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Zi-Xue
authors.initials: ZX
authors.lastname: Xuan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Lin-Na
authors.initials: LN
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Cheng-Wang
authors.initials: CW
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: De-Xuan
authors.initials: DX
authors.lastname: Yang
authors.affiliation: Department of Production Technology, Shandong Buchang Shenzhou Pharmaceutical Co., Ltd., Heze 274000, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Ying-Hong
authors.initials: YH
authors.lastname: An
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Production Technology, Shandong Buchang Shenzhou Pharmaceutical Co., Ltd., Heze 274000, P.R. China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Li
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
authors.forename: Shou-Jun
authors.initials: SJ
authors.lastname: Yuan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2