title: An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth.
abstract: Lung cancer is the leading cause of mortality and 5-year survival rate is very low worldwide. Recent studies show that vascular endothelial growth factor receptor-3 (VEGFR-3) signaling pathway contributes to lung cancer progression. So we hypothesize that an oral DNA vaccine that targets VEGFR-3 carried by attenuated Salmonella enterica serovar typhimurium strain SL3261 has impacts on lung cancer progression. In this study, the oral VEGFR-3-based vaccine-immunized mice showed appreciable inhibition of tumor growth and tumor lymphatic microvessels in lung cancer mice model. Moreover, the oral VEGFR-3-based vaccine-immunized mice showed remarkable increases in both VEGFR-3-specific antibody levels and cytotoxic activity. Furthermore, the oral VEGFR-3-based vaccine-immunized mice showed a significant increase in the levels of T helper type 1 (Th1) cell intracellular cytokine expression (IL-2, IFN-γ, and TNF-α). After inoculation with murine Lewis lung carcinoma (LLC) cells, CD4(+) or CD8(+) T cell numbers obviously declined in control groups whereas high levels were maintained in the oral VEGFR-3-based vaccine group. These results demonstrated that the oral VEGFR-3-based vaccine could induce specific humoral and cellular immune responses and then significantly inhibit lung carcinoma growth via suppressing lymphangiogenesis.
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Cong Guo
authors.initials: CG
authors.lastname: Jin
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Yong Chun
authors.initials: YC
authors.lastname: Zhou
authors.affiliation: Princess Margaret Cancer Center and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada.
authors.forename: Roya
authors.initials: R
authors.lastname: Navab
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Kristine Raaby
authors.initials: KR
authors.lastname: Jakobsen
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Xiao Qun
authors.initials: XQ
authors.lastname: Chen
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Ting Ting
authors.initials: TT
authors.lastname: Li
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Luo
authors.affiliation: Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China. wangxc2005323@126.com.|Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China. wangxc2005323@126.com.|Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China. wangxc2005323@126.com.
authors.forename: Xi Cai
authors.identifier: http://orcid.org/0000-0002-2130-1887
authors.initials: XC
authors.lastname: Wang
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D019556:COS Cells; D019496:Cancer Vaccines / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D018450:Disease Progression; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology*; D042583:Lymphangiogenesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D019779:Salmonella enterica / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D007371:Interferon-gamma; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: Attenuated Salmonella enterica serovar Typhimurium; DNA vaccine; Lung cancer; Lymphangiogenesis; VEGFR-3