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Hidenori Takahashi, Hidenobu Ishizaki, Hideaki Tahara, Yasuhiro Tamaki, Yasuo Yanagi; Suppression of Choroidal Neovascularization by Vaccination with Epitope Peptide Derived from Human VEGF Receptor 2 in an Animal Model. Invest. Ophthalmol. Vis. Sci. 2008;49(5):2143-2147. doi: 10.1167/iovs.07-0523.
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purpose. It has been shown that vaccination with peptides derived from human vascular endothelial growth factor receptor 2 (VEGFR2) induces cytotoxic T lymphocytes (CTLs) with potent cytotoxicity against endothelial cells expressing VEGFR2 in a A2/Kb transgenic mice system expressing human HLA-A*0201. The present study examined the efficacy of this immunotherapy against age-related macular degeneration (AMD) using a choroidal neovascularization (CNV) model.
methods. Seven- to 10-week-old A2/Kb transgenic mice expressing human HLA-A*0201 were used. The mice were divided into three groups of 15 animals each: phosphate-buffered saline (PBS) treatment (control); immunity adjuvant (incomplete Freund adjuvant [IFA]); and antigen peptide of human VEGFR 2 and IFA (peptide vaccination group). Immunization was given on days 0 and 11. On day 20, six CNVs were induced in both eyes of each animal using a semiconductor laser set to 75 μm, 200 mW, and 0.05 seconds. Leakage from the CNV was measured by fluorescein angiography 7 days after laser treatment. CNV volume was measured using a choroidal flatmount after perfusing the mice with fluorescein conjugate lectin.
results. There were no significant differences in the leakage or the area of CNV in the IFA-treated group compared with controls. In contrast, the fluorescent leakage index in the peptide vaccination group was reduced to 80% and the CNV area to 18% compared with the control group (P < 0.0001 and P < 0.05, respectively).
conclusions. This model provides a rationale for immunotherapy using the epitope peptides derived from VEGFR2 for the treatment of CNV.
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