title: Development of novel DNA vaccine for VEGF in murine cancer model.
abstract: We developed DNA vaccine for vascular endothelial growth factor (VEGF), which may provide the therapeutic option instead of anti-VEGF antibody, bevacizumab. Plasmid containing VEGF mini-gene was constructed in the insertion of B-cell epitope of Hepatitis B core protein [HBc-VEGF], which was an epitope carrier. High titer of anti-VEGF antibody was observed in BALB/c mice which were intramuscularly immunized with HBc-VEGF by electropolator. In mice inoculated with colon 26 cells, tumor volume and microvessel density was decreased in HBc-VEGF with a significant prolonged survival. Co-treatment of purified IgG from immunized mice with HBc-VEGF showed in vitro neutralizing activity for VEGF-induced ERK phosphorylation and tube formation in cultured endothelial cells. Furthermore, intravitreally injection of this purified IgG reduced the neovessel formation in the mouse oxygen-induced retinopathy and laser-induced choroidal neovascularization models. These results first provided that DNA vaccine against VEGF possessed the anti-angiogenic effect, leading to prolonged survival in mouse cancer model.
authors.affiliation: 1] Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine [2] Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, Hamamatsu University School of Medicine, Chiba University and Fukui University.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kyutoku
authors.forename: Hironori
authors.initials: H
authors.lastname: Nakagami
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Koriyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Tomioka
authors.forename: Futoshi
authors.initials: F
authors.lastname: Nakagami
authors.forename: Munehisa
authors.initials: M
authors.lastname: Shimamura
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kurinami
authors.forename: Pang
authors.initials: P
authors.lastname: Zhengda
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Jo
authors.forename: Jeong Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
mesh_terms: D020533:Angiogenesis Inhibitors / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000494:pharmacology; D000068258:Bevacizumab; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000276:immunology; D010957:Plasmids / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018985:Epitopes, B-Lymphocyte; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab