A Novel Bispecific Anti-IL17/VEGF Fusion Trap Exhibits Potent and Long-Lasting Inhibitory Effects on the Development of Age-Related Macular Degeneration.

Abstract

Age-related macular degeneration (AMD) is a severe eye disease in people aged 60 years and older. Although anti-VEGF therapies are effective in treating neovascular AMD (NvAMD) in the clinic, up to 60% of patients do not completely respond to the therapies. Recent studies have shown that blood-derived macrophages and their associated proinflammatory cytokines may play important roles in the development of persistent disease and resistance to anti-VEGF therapy. To address this issue, we constructed an antibody-based bispecific fusion protein that can simultaneously inhibit IL-17-induced inflammation and VEGF-mediated neovascularization. As a result, the bispecific fusion protein 17V05 effectively inhibited multiple proinflammatory cytokines and chemokines, as well as laser-induced choroidal neovascularization (CNV). More importantly, 17V05 also exhibited stronger and longer inhibitory effects than conbercept in vivo. Thus, we provide a novel and promising strategy for treating AMD patients who are not sensitive to anti-VEGF therapies.