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

• DOI: 10.1007/s13277-015-4061-3
• Publication Date: 2015-09-16T13:11:03Z
• Authors: Yan Chen; Xin Liu; Cong Guo Jin; Yong Chun Zhou; Roya Navab; Kristine Raaby Ja...; Xiao Qun Chen; Jia Li; Ting Ting Li; Lu Luo; Xi Cai Wang
• Keywords: DNA vaccine; Lung Neoplasms; Adaptive Immunity; Vaccines, Attenuated; Cancer Vaccines; Interferon-gamma; Mice; 03 medical and health sciences; Cell Line, Tumor; Chlorocebus aethiops; Animals; Lymphangiogenesis; Attenuated Salmonella enterica serovar Typhimurium; 0303 health sciences; Tumor Necrosis Factor-alpha; Carcinoma; Salmonella enterica; Th1 Cells; 3. Good health; VEGFR-3; Mice, Inbred C57BL; COS Cells; Disease Progression; Interleukin-2; Female; Lung cancer; Signal Transduction

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.