JOURNAL ARTICLE

Suppression of choroidal neovascularization by vaccination with epitope peptide derived from human VEGF receptor 2 in an animal model

Hidenori Takahashi, Hidenobu Ishizaki, Hideaki Tahara, Yasuhiro Tamaki, Yasuo Yanagi
Investigative Ophthalmology & Visual Science 2008, 49 (5): 2143-7
18436847

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 mum, 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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