title: A bispecific antibody effectively inhibits tumor growth and metastasis by simultaneous blocking vascular endothelial growth factor A and osteopontin.
abstract: Both vascular endothelial growth factor A (VEGF) and osteopontin (OPN) can directly induce tumor angiogenesis, which is essential for the growth and metastasis of solid tumors. Here we engineered a bispecific antibody (VEGF/OPN-BsAb) using the anti-VEGF-A antibody bevacizumab and the anti-OPN antibody hu1A12. Compared with hu1A12 alone and bevacizumab alone, VEGF/OPN-BsAb was significantly more effective in inhibiting tumor angiogenesis in a highly metastatic human hepatocellular carcinoma nude mouse model. Further study demonstrated that VEGF/OPN-BsAb could effectively suppress primary tumor growth and metastasis to lungs, suggesting that it might be a promising therapeutic agent for treatment of metastatic cancer.
authors.affiliation: International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, People's Republic of China.
authors.forename: Geng
authors.initials: G
authors.lastname: Kou
authors.forename: Jingping
authors.initials: J
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Dapeng
authors.initials: D
authors.lastname: Zhang
authors.forename: Sheng
authors.initials: S
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Zhao
authors.forename: Chen
authors.initials: C
authors.lastname: Fang
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Xunming
authors.initials: X
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Liang
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Bohua
authors.initials: B
authors.lastname: Li
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016466:CHO Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D006801:Humans; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D008175:Lung Neoplasms / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology / Q000517:prevention & control*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D053495:Osteopontin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D011485:Protein Binding / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D000068258:Bevacizumab