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Tumour Biol. 2016 Feb;37(2):2395-404. doi: 10.1007/s13277-015-4061-3. Epub 2015 Sep 16.

An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth.

Chen Y1,2,3, Liu X1,2,3, Jin CG1,2,3, Zhou YC1,2,3, Navab R4, Jakobsen KR5, Chen XQ1,2,3, Li J1,2,3, Li TT1,2,3, Luo L1,2,3, Wang XC6,7,8.

Author information

1
Yunnan Tumor Institute, The Third Affiliated Hospital of Kunming Medical University (Tumor Hospital of Yunnan Province), 519 Kunzhou Road, Kunming, Yunnan, China.
2
Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China.
3
Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China.
4
Princess Margaret Cancer Center and Campbell Family Institute for Cancer Research, University Health Network, Toronto, Ontario, Canada.
5
Department of Biomedicine, Aarhus University, Aarhus, Denmark.
6
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.
7
Yunnan Tumor Molecular Biomarker Research Center, Kunming, Yunnan, China. wangxc2005323@126.com.
8
Yunnan Zhan Qimin Academician Workstation, Kunming, Yunnan, China. wangxc2005323@126.com.

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.

KEYWORDS:

Attenuated Salmonella enterica serovar Typhimurium; DNA vaccine; Lung cancer; Lymphangiogenesis; VEGFR-3

PMID:
26376999
DOI:
10.1007/s13277-015-4061-3
[Indexed for MEDLINE]

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