Combined effects of oncolytic vaccinia virus and dendritic cells on the progression of melanoma B16-F10 in mice

Abstract

Aim: We aimed to test the hypothesis that loading of dendritic cells (DCs) with both viral and tumor-specific antigens would enhance the efficacy antitumor DC-based therapy applied simultaneously with oncolytic virus. Methods: Vaccinia virus LIVP/GFP and melanoma B16-F10 were used in this study. DCs were pulsed with various combinations of viral and tumor-associated antigens. The maturation status of DCs was verified by expression of the markers CD80, CD86, and CCR7 and assessment of IL-6, TNF-α, and IL-12 secretion. The most efficient combination of antigens for DC loading was selected based on the analysis of the cytotoxic activity of T lymphocytes. Combination therapy using vaccinia virus LIVP/GFP and DCs pulsed with viral and tumor-specific antigens was administered to the B16-F10 melanoma/mouse C57Bl tumor model. Results: We found that loading of DCs with viral antigens, or with a combination of viral and tumor antigens, resulted in similar levels of expression of DC maturation markers. The maximal in vitro cytotoxicity against virus-infected and non-infected B16 melanoma cells exhibited T lymphocytes activated by DCs loaded with the heat inactivated lysate of vaccinia virus LIVP/GFP infected tumor cell. The results show that the combination of vaccinia virus LIVP/GFP and DCs loaded with both tumor and viral antigens inhibit tumor growth of B16-F10 murine melanoma by more than two-fold. Conclusions: Combination therapy with oncolytic vaccinia virus LIVP/GFP and tumor/virus antigen-loaded DCs limited the growth of established melanoma B16-F10, but no synergistic antitumor effects were observed. We propose that optimization of the therapy regimen could enhance the efficiency of combination therapy.