Recombinant humanized anti-vascular endothelial growth factor monoclonal antibody efficiently suppresses laser-induced choroidal neovascularization in rhesus monkeys

Abstract

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.

Keywords: Alamar blue (PubChem CID: 11,077); CNV; FITC (PubChem CID: 259,101); Hematoxylin-eosin (PubChem CID: 86,598,188); Monoclonal antibody; Pentobarbital sodium (PubChem CID: 23,676,152); RabMAb; Sodium hydroxide (PubChem CID: 14,798); VEGF; Wet AMD.