A bispecific antibody effectively inhibits tumor growth and metastasis by simultaneous blocking vascular endothelial growth factor A and osteopontin

Geng Kou; Jingping Shi; Lin Chen; Dapeng Zhang; Sheng Hou; Lei Zhao; Chen Fang; Lei Zheng; Xunming Zhang; Ping Liang; Xu Zhang; Bohua Li; Yajun Guo

doi:10.1016/j.canlet.2010.08.011

A bispecific antibody effectively inhibits tumor growth and metastasis by simultaneous blocking vascular endothelial growth factor A and osteopontin

Cancer Lett. 2010 Dec 28;299(2):130-6. doi: 10.1016/j.canlet.2010.08.011. Epub 2010 Sep 9.

Authors

Geng Kou¹, Jingping Shi, Lin Chen, Dapeng Zhang, Sheng Hou, Lei Zhao, Chen Fang, Lei Zheng, Xunming Zhang, Ping Liang, Xu Zhang, Bohua Li, Yajun Guo

Affiliation

¹ International Joint Cancer Institute, The Second Military Medical University, Shanghai 200433, People's Republic of China.

PMID: 20826049
DOI: 10.1016/j.canlet.2010.08.011

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Antibodies, Bispecific / immunology
Antibodies, Bispecific / pharmacology*
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal, Humanized
Bevacizumab
CHO Cells
Cell Line, Tumor
Cell Proliferation / drug effects
Cells, Cultured
Cricetinae
Cricetulus
Female
Humans
Kinetics
Liver Neoplasms, Experimental / pathology
Liver Neoplasms, Experimental / prevention & control
Lung Neoplasms / prevention & control
Lung Neoplasms / secondary
Mice
Mice, Inbred BALB C
Mice, Nude
Neoplasms / pathology
Neoplasms / prevention & control*
Neovascularization, Pathologic / prevention & control
Osteopontin / antagonists & inhibitors*
Osteopontin / genetics
Osteopontin / immunology
Protein Binding / immunology
Reverse Transcriptase Polymerase Chain Reaction
Tumor Burden / drug effects
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor A / genetics
Vascular Endothelial Growth Factor A / immunology
Xenograft Model Antitumor Assays

Substances

Antibodies, Bispecific
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Vascular Endothelial Growth Factor A
Osteopontin
Bevacizumab

Abstract

Publication types

MeSH terms

Substances

Grants and funding