A Monotargeting Peptidic Network Antibody Inhibits More Receptors for Anti-Angiogenesis

Area of Science:

• Biomedical Engineering
• Ophthalmology
• Molecular Biology

Background:

• Corneal neovascularization (CNV) involves abnormal blood vessel growth driven by growth factors and receptors on endothelial cells (ECs).
• Current treatments like monoclonal antibodies (e.g., bevacizumab) typically target only one growth factor or receptor, limiting efficacy.

Purpose of the Study:

• To develop a novel monotargeting peptidic network antibody (pepnetibody) for high-efficiency treatment of CNV.
• To investigate the mechanism of pepnetibody in blocking multiple endothelial cell receptors and its antiangiogenesis effects.

Main Methods:

• Development of a peptidic network antibody (pepnetibody) capable of in situ fibrillogenesis on EC membranes.
• Evaluation of pepnetibody's binding to integrin α_vβ₃ and its ability to block other angiogenesis-related receptors (VEGF receptor-2, neuropilin-1).
• Comparison of pepnetibody's antiangiogenesis efficacy against bevacizumab in CNV models.

Main Results:

• Pepnetibody forms a fibrous network on ECs, mimicking fibronectin fibrillogenesis.
• The in situ formed network effectively blocks integrin α_vβ₃ and covers other key angiogenesis receptors.
• Pepnetibody demonstrated competitive antiangiogenesis efficacy compared to bevacizumab at 97.7 times lower doses.

Conclusions:

• Pepnetibody represents a promising new therapeutic strategy for corneal neovascularization.
• Its ability to simultaneously block multiple receptors offers superior antiangiogenesis potential.
• The significantly reduced dosage requirement highlights its potential for improved safety and efficacy.