Recombinant humanized anti-vascular endothelial growth factor monoclonal antibody efficiently suppresses laser-induced choroidal neovascularization in rhesus monkeys
| Autor: | Peng Yang, Fang Peng, Yu-Xia Cao, Hu Li, Shou-Sheng Yan, Ning Xie, Dong-An Yu, Wan-Wan Ji |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Vascular Endothelial Growth Factor A
0301 basic medicine genetic structures medicine.drug_class medicine.medical_treatment Pharmaceutical Science Pharmacology Antibodies Monoclonal Humanized Monoclonal antibody Mice 03 medical and health sciences 0302 clinical medicine Retinal Diseases Human Umbilical Vein Endothelial Cells medicine Animals Humans Cells Cultured Cell Proliferation Retina biology Chemistry Lasers Growth factor Macular degeneration medicine.disease Macaca mulatta Choroidal Neovascularization Recombinant Proteins eye diseases Oxygen 030104 developmental biology Choroidal neovascularization medicine.anatomical_structure Immunology 030221 ophthalmology & optometry biology.protein sense organs medicine.symptom Antibody Receptor antagonist activity Retinopathy |
| Zdroj: | European Journal of Pharmaceutical Sciences. 109:624-630 |
| ISSN: | 0928-0987 |
| DOI: | 10.1016/j.ejps.2017.09.021 |
| Popis: | Neovascular age-related macular degeneration, characterized by abnormal choroidal neovascularization (CNV), is a major cause of blindness worldwide. Anti-vascular endothelial growth factor (VEGF) antibodies have demonstrated significant efficacy in improving visual acuity. TMAB001 is a new recombinant humanized rabbit anti-VEGF monoclonal antibody. It presents high activities in vitro studies. In the binding affinity assay, TMAB001 exhibited a high binding capability to VEGF with an affinity constant of 10-11M. In the receptor antagonist activity assay, IC50 of TMAB001 was 0.15μg/ml. In a cell-based assay, TMAB001 inhibited VEGF165-induced HUVEC cells proliferation in a dose-dependent manner. Furthermore, in the rhesus monkey model of laser-induced CNV, results showed the growth and leakage of experimental CNV were significantly decreased with a single bilateral intravitreal injection of TMAB001, and the grade 4 lesions were complete absence in TMAB001 groups. The efficacy of TMAB001 was maintained for at least 28days. In a mice model of oxygen-induced retinopathy, the retina fluorescence leakage was reduced and the vascular morphology in retina was normalized by TMAB001 intraperitoneal administration. In conclusion, those results indicate that TMAB001 might be a potential drug candidate for wet AMD. |
| Databáze: | OpenAIRE |
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