Vaccination with Melanoma Cells Infected with Recombinant Newcastle Disease Virus Suppresses Tumor Metastasis

Abstract

Newcastle Disease Virus (NDV) is an RNA virus, which infects several tumor cells and shows cellular toxicity towards them. The antitumor activity of NDV has been reported in several tumors. In this study, we evaluated the antitumor effect of a NDV-infected melanoma cell vaccine on lung metastasis based on tumor-specific immune responses in a mouse model. B16 mouse melanoma cells were infected with the GFP-expressing recombinant NDV (rNDV) to prepare the vaccine (rNDV-BV). C57BL/6 mice were then immunized twice with rNDV-BV and intravenously inoculated with B16 cells, and the number of metastasis dots in the lungs was evaluated 21 days later. The mice were divided into three groups: pre-inoculation (mice were vaccinated before inoculation with B16 cells), post-inoculation (mice were vaccinated after inoculation with B16 cells), and control (mice were inoculated with DMEM) groups. To evaluate the immune responses, the mouse splenocytes were monitored for lymphocyte subsets and dendritic cells, and IFN-γ and IL-10gene expression after metastasis was measured. The mice receiving rNDV-BV showed prolonged survival and a lower number of metastasis dots. Furthermore, lung metastasis was significantly decreased upon post-metastasis vaccination with rNDV-BV. In pre-inoculation group, cytokine responses against tumor antigens were also significantly affected: IFN-γ levels were increased, but IL-10 levels were decreased. The vaccination also increased the T cell population along with the number of CD8+ dendritic cells during early metastasis. These results indicated that rNDV-BV induced an IFN-γ response against the tumor antigen and suppressed metastasis in the mouse model. Keywords: Autologous-tumor Vaccine; Newcastle Disease Virus; Melanoma Lung Metastasis Mouse Model; Cell-Mediated Immunity; IFN-γ; Abbreviations: NDV: Newcastle Disease Virus; rNDV: Recombinant Newcastle Disease Virus; rNDV-BV: Recombinant Newcastle Disease Virus to Prepare the Vaccine; B16: B16 Mouse Melanoma Cell; IFN: Interferon; IL: Interleukin.