Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable...

Area of Science:

• Biochemistry
• Molecular Biology
• Ophthalmology

Background:

• Vascular Endothelial Growth Factor (VEGF) family factors are key drivers of abnormal angiogenesis in tumors and ocular diseases.
• VEGF inhibition is a primary strategy in antiangiogenic therapy.
• Conbercept is a novel fusion protein combining VEGF receptor extracellular domains with human immunoglobulin's Fc region.

Purpose of the Study:

• To evaluate conbercept's binding affinity to VEGF isoforms and Placental Growth Factor (PlGF).
• To compare conbercept's efficacy against VEGF-A, VEGF-B, and PlGF with the anti-VEGF antibody Avastin.
• To assess conbercept's in vivo anti-angiogenic and anti-tumor effects.

Main Methods:

• Surface plasmon resonance (BIACORE) and Enzyme-Linked Immunosorbent Assay (ELISA) were used to determine binding affinities.
• Oxygen-induced retinopathy model in mice was employed to evaluate neovascularization inhibition.
• Tumor growth suppression was assessed in tumor-bearing nude mice.

Main Results:

• Conbercept exhibited higher binding affinity to VEGF-A isoforms compared to Avastin.
• Conbercept demonstrated binding to VEGF-B and PlGF, which Avastin did not.
• In vivo studies showed conbercept effectively inhibited neovascularization and suppressed tumor growth.

Conclusions:

• Conbercept binds with high affinity to multiple VEGF isoforms and PlGF.
• Conbercept possesses significant anti-angiogenic properties, validated in preclinical models.
• Conbercept shows promise as a therapeutic agent for angiogenesis-related conditions, including cancer and wet Age-related Macular Degeneration (AMD).