Recombinant anti-vascular endothelial growth factor fusion protein efficiently suppresses choridal neovasularization in monkeys.

OBJECTIVE

KH902 is a fusion protein that combines the ligand binding elements derived from the extracellular domain of vascular endothelial growth factor (VEGF) receptors 1 and 2 and the Fc portion of IgG1. This study was designed to test the Cat Recombinant Proteins inhibitory effect of KH902 in a monkey model of choroidal neovascularization (CNV).

METHOD

Affinity binding to VEGF was measured using ELISA kits of human VEGF, and the effect of the biological activity of KH902 tested by in vitro inhibition experiments on human umbilical vein endothelial cell proliferation induced by VEGF. 

The experimental CNV induced by laser injury perimacular cause in the eyes of rhesus monkeys and confirmed by fluorescence fundus angiography (FFA), optical coherence tomography (OCT) and multifocal Electroretinograms (mf-ERG) 20 days after suffering from injury Laser. KH902 delivered to the animal via intravitreal injection at various doses. The monkeys were observed four weeks after injection with eye examination, FFA, October, mf-ERG, histopathological and immunohistochemical analysis.

RESULTS

KH902 high affinity binding of VEGF in the average IC (50) of 10:00. KH902 at 41 nM really can block VEGF-induced cell proliferation and KH902 at 10.7 nM can block 82.6% of cell growth. In the eyes of the treatment group, which received 300 microg and 500 microg KH902, choroidal neovascularization leak clearly less than before injection, and no leakage was observed at the end of the observation after injection. 

No high echogenic mass reflected light is detected by October However, in 0.1 mg KH902-treated and control eyes, and high leakage reflect light echogenic mass is still there. Experimental CNV greater reduction in eyes treated with 300 microg and 500 microg KH902 than in eyes treated with 0.1 mg of KH902 and control eyes. 

There is a proliferation vasculosa fiber membranes in 100 microg KH902-treated eyes and control eyes but in the eyes of 300 microg and 500 microg KH902-treated under observation histopathology. Mf-ERG Results showed that there was greater improvement in eye 300 microg and 500 microg KH902-treated than 100 microg KH902-treated eyes and control eyes.

CONCLUSION

KH902 gift with VEGF high affinity and inhibitory activity on the proliferation of human umbilical vein endothelial cells (HUVECs) induced Fungal Recombinant Proteins by VEGF. A single 300 microg or 500 microg KH902 intravitreal injection effectively inhibit leakage and CNV growth in rhesus monkeys with no evidence of toxicity. This study showed that KH902 has promise as a local antiangiogenic treatment of CNV.