title: Inhibition of tumor angiogenesis in lung cancer by T4 phage surface displaying mVEGFR2 vaccine.
abstract: Vascular endothelial growth factor (VEGF) has been known as a potential vasculogenic and angiogenic factor and its receptor (VEGFR2) is a major receptor to response to the angiogenic activity of VEGF. The technique that to break the immune tolerance of "self-antigens" associated with angiogenesis is an attractive approach for cancer therapy with T4 phage display system. In this experiment, mouse VEGFR2 was constructed on T4 phage nanometer-particle surface as a recombinant vaccine. T4-mVEGFR2 recombinant vaccine was identified by PCR and western blot assay. Immunotherapy with T4-mVEGFR2 was confirmed by protective immunity against Lewis lung carcinoma (LLC) in mice. The antibody against mVEGFR2 was detected by ELISPOT, ELISA and Dot ELISA. The inhibitive effects against angiogenesis were studied using CD31 and CD105 via histological analysis. VEGF-mediated endothelial cells proliferation and tube formation were inhibited in vitro by immunoglobulin induced by T4-mVEGFR2. The antitumor activity was substantiated from the adoptive transfer of the purified immunoglobulin. Antitumor activity and autoantibody production of mVEGFR2 could be neutralized by the depletion of CD4+T lymphocytes. These studies strongly suggest that T4-mVEGFR2 recombinant vaccine might be a promising antitumor approach.
authors.affiliation: Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Shunxiang
authors.initials: S
authors.lastname: Ren
authors.lastname: Fengyu
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zuo
authors.forename: Minyi
authors.initials: M
authors.lastname: Zhao
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
authors.forename: Xicai
authors.initials: X
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Wu
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Ren
mesh_terms: D019264:Adoptive Transfer; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000818:Animals; D017122:Bacteriophage T4 / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000276:immunology / Q000628:therapy; D049109:Cell Proliferation; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D007167:Immunotherapy / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood; D008175:Lung Neoplasms / Q000098:blood supply / Q000276:immunology / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage* / Q000276:immunology*
chemical_list: D020533:Angiogenesis Inhibitors; D019496:Cancer Vaccines; D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D040301:Vascular Endothelial Growth Factor Receptor-2