Inhibition of tumor angiogenesis in lung cancer by T4 phage surface displaying mVEGFR2 vaccine

Shunxiang Ren; Fengyu; Shuguang Zuo; Minyi Zhao; Xiaobin Wang; Xicai Wang; Yan Chen; Zhiping Wu; Zhaojun Ren

doi:10.1016/j.vaccine.2011.03.051

Inhibition of tumor angiogenesis in lung cancer by T4 phage surface displaying mVEGFR2 vaccine

Vaccine. 2011 Aug 5;29(34):5802-11. doi: 10.1016/j.vaccine.2011.03.051. Epub 2011 Apr 9.

Authors

Shunxiang Ren¹, Fengyu, Shuguang Zuo, Minyi Zhao, Xiaobin Wang, Xicai Wang, Yan Chen, Zhiping Wu, Zhaojun Ren

Affiliation

¹ Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China.

PMID: 21482223
DOI: 10.1016/j.vaccine.2011.03.051

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.

MeSH terms

Adoptive Transfer
Angiogenesis Inhibitors / administration & dosage
Animals
Bacteriophage T4 / genetics
Bacteriophage T4 / immunology
CD4-Positive T-Lymphocytes / metabolism
Cancer Vaccines / administration & dosage
Cancer Vaccines / immunology
Cancer Vaccines / pharmacology
Carcinoma, Lewis Lung* / blood supply
Carcinoma, Lewis Lung* / immunology
Carcinoma, Lewis Lung* / therapy
Cell Proliferation
Endoglin
Endothelial Cells / metabolism
Enzyme-Linked Immunosorbent Assay
Enzyme-Linked Immunospot Assay
Immunotherapy / methods
Intracellular Signaling Peptides and Proteins / blood
Lung Neoplasms / blood supply
Lung Neoplasms / immunology
Lung Neoplasms / therapy
Mice
Mice, Inbred C57BL
Neovascularization, Pathologic* / immunology
Neovascularization, Pathologic* / prevention & control
Neovascularization, Pathologic* / therapy
Platelet Endothelial Cell Adhesion Molecule-1 / blood
Recombinant Fusion Proteins / administration & dosage
Recombinant Fusion Proteins / immunology
Vaccines, Synthetic* / administration & dosage
Vaccines, Synthetic* / immunology
Vaccines, Synthetic* / pharmacology
Vascular Endothelial Growth Factor Receptor-2 / administration & dosage*
Vascular Endothelial Growth Factor Receptor-2 / immunology*

Substances

Angiogenesis Inhibitors
Cancer Vaccines
Endoglin
Eng protein, mouse
Intracellular Signaling Peptides and Proteins
Platelet Endothelial Cell Adhesion Molecule-1
Recombinant Fusion Proteins
Vaccines, Synthetic
Vascular Endothelial Growth Factor Receptor-2