Ranibizumab inhibits multiple forms of biologically active vascular endothelial growth factor in vitro and in vivo
| Autor: | Vanessa Shiu, Valerie Quarmby, John B. Lowe, Mauricio Maia, Amy Oldendorp, Jihong Yang, Mike Reich, Jacques Gaudreault, Henry B. Lowman, James Araujo, Samantha Lien |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Vascular Endothelial Growth Factor A
genetic structures Guinea Pigs Vascular permeability Angiogenesis Inhibitors Pharmacology Antibodies Monoclonal Humanized Capillary Permeability Cellular and Molecular Neuroscience chemistry.chemical_compound In vivo Ranibizumab Medicine Animals Humans Cells Cultured Cell Proliferation Skin Dose-Response Relationship Drug business.industry Antibodies Monoclonal Biological activity Macular degeneration medicine.disease Sensory Systems Recombinant Proteins Vascular endothelial growth factor Ophthalmology Vascular endothelial growth factor A chemistry Human umbilical vein endothelial cell Endothelium Vascular business medicine.drug |
| Zdroj: | Experimental eye research. 85(4) |
| ISSN: | 0014-4835 |
| Popis: | Neovascular age-related macular degeneration (AMD) is the leading cause of blindness in older adults in the Western world. Ranibizumab (Lucentis), a humanized antibody fragment directed against vascular endothelial growth factor (VEGF-A), was recently approved by the US Food and Drug Administration (FDA) for the treatment of neovascular AMD. The objective of this study was to characterize the binding affinity and pharmacological activity of ranibizumab for 3 biologically active forms of VEGF-A: VEGF165, VEGF121, and VEGF110. The apparent equilibrium binding affinity of ranibizumab for VEGF-A molecules was determined by Biacore analysis; the biological activity of VEGF-A was demonstrated in a human umbilical vein endothelial cell (HUVEC) proliferation-inhibition assay. Inhibition of VEGF-A-induced vascular permeability by ranibizumab was assessed in vivo using hairless guinea pigs and a modified Miles assay. Ranibizumab was capable of binding to recombinant human VEGF165, VEGF121, and VEGF110 (KD < or = 192 pM), inhibiting VEGF-A-induced HUVEC proliferation in a concentration-dependent manner. Ranibizumab also exerted potent dose-dependent inhibition (IC(50) of 0.4-1.2 nM) of the vascular permeability-enhancing activity of VEGF165, VEGF121, and VEGF110 in the Miles assay. In conclusion, these results show that ranibizumab is capable of binding to and specifically inhibiting the activities of 3 biologically active forms of VEGF-A. As VEGF-A plays a pivotal role in the pathogenesis of neovascular AMD, ranibizumab activity, as demonstrated in this study, supports its clinical utility in the treatment of this disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect