Immunization with synthetic VEGF peptides in ovarian cancer.
OBJECTIVE
To assess the role of active immunotherapy targeting VEGF with a peptide vaccine as a potential treatment for ovarian cancer.


METHODS
A peptide vaccine targeting antigenic B-cell epitopes of VEGF were identified and linked to a promiscuous T-cell epitope. Elicited antibodies were assessed for their ability to recognize the VEGF protein, inhibit angiogenesis, inhibit the interaction of VEGF with its receptor, and inhibit cancer growth in mice.


RESULTS
Following immunization, high-titered elicited antibodies were shown to be specific for the full-length VEGF protein by ELISA and Western blot. Anti-VEGF peptide antibodies inhibited cellular migration, proliferation, invasion, tube formation, and growth of aortic ring cultures. These antibodies inhibited the interaction between VEGF and its receptor (VEGFR2) in a concentration-dependent manner. Confirmation of this mechanism was demonstrated through inhibition of VEGFR2 phosphorylation following culture of human endothelial vein endothelial cells with anti-VEGF peptide antibodies. These antibodies were shown to inhibit ovarian cancer xenograft growth in a nude mouse model following intraperitoneal passive immunization. Active immunization with the VEGF peptide vaccine inhibited VEGF-dependent pancreatic islet cell tumor growth in RIP1-Tag2 transgenic mice and was associated with decreased vasculogenesis in these tumors compared with animals vaccinated with an irrelevant peptide. Active immunization also inhibited growth of tumors from a VEGF overexpressing ovarian cancer cell line, resulting in decreased tumor size and tumor vessel density compared with control mice.


CONCLUSIONS
Active immunization with VEGF peptides elicits antibodies that inhibit tumor growth by blocking VEGF-dependent angiogenesis.
Wang
Bing
B
College of Biological Sciences, Department of Microbiology and Medicinal Biochemistry, The Ohio State University College of Medicine and Comprehensive Cancer Center, Columbus, OH 43210, USA.
Kaumaya
Pravin T P
PT
Cohn
David E
DE
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D029122:Murine pneumonia virus; D009389:Neovascularization, Pathologic / Q000276:immunology; D010051:Ovarian Neoplasms / Q000098:blood supply / Q000276:immunology / Q000628:therapy*; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D011817:Rabbits; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D000906:Antibodies; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D042461:Vascular Endothelial Growth Factor A
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