An orally administered DNA vaccine targeting vascular endothelial growth factor receptor-3 inhibits lung carcinoma growth
- 190 Downloads
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.
KeywordsLung cancer Lymphangiogenesis VEGFR-3 DNA vaccine Attenuated Salmonella enterica serovar Typhimurium
This study was funded by grants from the National Natural Science Foundation of China (No. 81460358, No. 81060177, No. 81460441), the Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University (No. 2012FB067), and the Yunnan Provincial Technology Project of Health (No. 2012WS0041, No. 2014NS024).
Compliance with ethical standards
Conflicts of interest
All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- 15.Hu J, Cheng Y, Li Y, Jin Z, Pan Y, Liu G, et al. MicroRNA-128 plays a critical role in human non-small cell lung cancer tumourigenesis, angiogenesis and lymphangiogenesis by directly targeting vascular endothelial growth factor-C. Eur J Cancer. 2014;50(13):2336–50. doi:10.1016/j.ejca.2014.06.005.CrossRefPubMedGoogle Scholar
- 17.Tiriveedhi V, Tucker N, Herndon J, Li L, Sturmoski M, Ellis M, et al. Safety and preliminary evidence of biologic efficacy of a mammaglobin-a DNA vaccine in patients with stable metastatic breast cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2014;20(23):5964–75. doi:10.1158/1078-0432.CCR-14-0059.CrossRefGoogle Scholar
- 39.Bogos K, Renyi-Vamos F, Dobos J, Kenessey I, Tovari J, Timar J, et al. High VEGFR-3-positive circulating lymphatic/vascular endothelial progenitor cell level is associated with poor prognosis in human small cell lung cancer. Clin Cancer Res Off J Am Assoc Cancer Res. 2009;15(5):1741–6. doi:10.1158/1078-0432.CCR-08-1372.CrossRefGoogle Scholar