Abstract
The blockade of VEGF pathway has been clinically validated as an initial treatment for renal cell carcinoma (RCC). Angiopoietin-2 (Ang-2) has been indicated as a key regulator for angiogenesis escape. The effect of a novel bispecific antibody (A2V CrossMab) against both Ang-2 and VEGF was investigated in comparison with either factor. A2V CrossMab significantly reduced tumor volume, vessel density, and interstitial fluid pressure compared to either monotherapy of anti-VEGF or anti-Ang-2. Host-derived angiogenesis-related genes have been significantly down-regulated in A2V CrossMab group. These data demonstrate that A2V CrossMab has additive anti-tumor effect for the treatment of RCC.
Keywords:
Angiopoietin; Anti-angiogenic therapy; Interstitial fluid pressure; Renal cell carcinoma; VEGF.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiopoietin-2 / antagonists & inhibitors
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Angiopoietin-2 / immunology*
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Angiopoietin-2 / metabolism
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Animals
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Antibodies, Bispecific / immunology
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Antibodies, Bispecific / pharmacology*
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Carcinoma, Renal Cell / drug therapy*
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Carcinoma, Renal Cell / genetics
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Cluster Analysis
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Female
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Kidney Neoplasms / drug therapy*
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Kidney Neoplasms / genetics
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Mice, Nude
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / genetics
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Vascular Endothelial Growth Factor A / antagonists & inhibitors
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Vascular Endothelial Growth Factor A / immunology*
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Vascular Endothelial Growth Factor A / metabolism
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Xenograft Model Antitumor Assays
Substances
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Angiopoietin-2
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Antibodies, Bispecific
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Vascular Endothelial Growth Factor A