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H. Takahashi, H. Ishizaki, Y. Yanagi, Y. Tamaki, H. Tahara; Immunotherapy Using the Epitope Peptides Derived From Vascular Endothelial Growth Factor Receptor 2 Suppresses Choroidal Neovascularization in a Mouse Model. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1771.
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Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors has become a chief choice of drug therapy for exudative age-related macular degeneration (AMD) due to choroidal neovascularization (CNV). Currently available anti-VEGF drugs require repetitive injection at a 4 to 6 weeks interval. Although the complication resulting from intravitreal injection is rare, risk of severe complication remains a main concern. It was shown that vaccination using peptides derived from human VEGF receptor 2 induces cytotoxic T lymphocyte (CTL) with potent cytotoxicity against endothelial cells expressing VEGFR2. The current study examined the efficacy of this immunotherapy against AMD using a mouse CNV model.
Seven to ten weeks old A2/Kb transgenic mice expressing human HLA-A*0201 were used. The mice were divided into three groups 1) PBS treatment (control) 2) immunity adjuvant (Incomplete Freund Adjuvant; IFA) and 3) the antigen peptide of human VEGF receptor 2 and IFA (peptide vaccination group: n = 15 in each group). Immunization was given on days 0 and day 10. On day 20, three CNVs were induced in both eyes of each animal using semiconductor laser under the condition of φ200µm, 200mW, and 0.02sec. The leakage from the CNV was measured by fluorescein angiography three days after the laser treatment (on day 23). CNV area was measured using choroidal flat mount after perfusing the mice by fluorescein conjugate lectin.
There were no significant differences in the leakage and the area of CNV in the IFA-treated group compared with controls. The fluorescent leakage index in peptide vaccination group was reduced to 18% compared to control group (p<0.05). The CNV area was reduced to 80% (p<0.0001) compared with the control group.
The immunotherapy using the epitope peptides derived from VEGFR2 could be used for antiangiogenic therapy in AMD.
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