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.Met...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.展开更多
基金This work was supported by the Russian Foundation for Basic Research project#18-34-20109Russian state budget of ICBFM SB RAS project#121031300044-5Russian Science Foundation RSF#19-74-30011.
文摘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.
