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Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Angiogenesis (London), 2012-06, Vol.15 (2), p.171-185 [Peer Reviewed Journal]

The Author(s) 2012 ;2015 INIST-CNRS ;Springer Science+Business Media B.V. 2012 ;ISSN: 0969-6970 ;EISSN: 1573-7209 ;DOI: 10.1007/s10456-011-9249-6 ;PMID: 22302382 ;CODEN: AGIOFT

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Title:
Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab
Author: Papadopoulos, Nicholas ; Martin, Joel ; Ruan, Qin ; Rafique, Ashique ; Rosconi, Michael P. ; Shi, Ergang ; Pyles, Erica A. ; Yancopoulos, George D. ; Stahl, Neil ; Wiegand, Stanley J.
Subjects: Angiogenesis Inhibitors - immunology ; Angiogenesis Inhibitors - pharmacology ; Antibodies, Monoclonal, Humanized - immunology ; Antibodies, Monoclonal, Humanized - pharmacology ; Bevacizumab ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Blood and lymphatic vessels ; Blood vessels and receptors ; Cancer Research ; Cardiology ; Cardiology. Vascular system ; Cell Biology ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endothelial Cells - immunology ; Endothelial Cells - metabolism ; Enzyme Activation - drug effects ; Fundamental and applied biological sciences. Psychology ; HEK293 Cells ; Humans ; Medical sciences ; Oncology ; Ophthalmology ; Original Paper ; Ranibizumab ; Receptors, Vascular Endothelial Growth Factor ; Recombinant Fusion Proteins - pharmacology ; Vascular Endothelial Growth Factor A - antagonists & inhibitors ; Vascular Endothelial Growth Factor A - immunology ; Vascular Endothelial Growth Factor A - metabolism ; Vascular Endothelial Growth Factor B - antagonists & inhibitors ; Vascular Endothelial Growth Factor B - immunology ; Vascular Endothelial Growth Factor B - metabolism ; Vascular Endothelial Growth Factor Receptor-1 - immunology ; Vascular Endothelial Growth Factor Receptor-1 - metabolism ; Vascular Endothelial Growth Factor Receptor-2 - immunology ; Vascular Endothelial Growth Factor Receptor-2 - metabolism ; Vertebrates: cardiovascular system
Is Part Of: Angiogenesis (London), 2012-06, Vol.15 (2), p.171-185
Description: Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.
Publisher: Dordrecht: Springer Netherlands
Language: English
Identifier: ISSN: 0969-6970
EISSN: 1573-7209
DOI: 10.1007/s10456-011-9249-6
PMID: 22302382
CODEN: AGIOFT
Source: MEDLINE
Alma/SFX Local Collection
SpringerOpen website
ProQuest Central

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Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

The Author(s) 2012 ;2015 INIST-CNRS ;Springer Science+Business Media B.V. 2012 ;ISSN: 0969-6970 ;EISSN: 1573-7209 ;DOI: 10.1007/s10456-011-9249-6 ;PMID: 22302382 ;CODEN: AGIOFT

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