Beschreibung:
Abstract VSV-GP, a novel chimeric Vesicular Stomatitis Virus (VSV) pseudotyped with the glycoprotein of the lymphocytic choriomeningitis virus represents a promising oncolytic virus (OV) that preferentially targets and kills cancer cells. Release of tumor antigens and activation of immune response by OV therapy might support dendritic cell (DC)-mediated anti-tumor immunity. Thus in our study we analyzed the efficacy and immune mechanisms of the combination of VSV-GP oncolytic virotherapy with DC-based immunotherapy. Combination of VSV-GP therapy and DC-based vaccination was investigated in the syngeneic subcutaneous B16-OVA melanoma model. SIINFEKL-loaded CpG-activated DCs (DCVacc) and VSV-GP were applied intra- and peritumorally and immune responses were analyzed in the spleen and tumor tissues. The DCVacc/VSV-GP combination therapy resulted in a significantly improved survival compared to single treatments. Surviving mice from the DCVacc/VSV-GP treated group showed a long lasting anti-tumor immunity against B16-OVA and partial anti-tumor immunity against non-OVA B16 melanoma in rechallenge experiments. Analyzing specific cytotoxic T lymphocyte (CTL) responses induced by DCVacc and VSV-GP single and combination treatments we found that both DCVacc and DCVacc/VSV-GP induced comparable levels of OVA-specific CD8+ T cell responses. In addition a strong VSV N peptide-specific CD8+ T cell response was found upon VSV-GP and DCVacc/VSV-GP treatments. The improved therapeutic effect by the DCVacc/VSV-GP combination treatment correlated with increased numbers of tumor infiltrating lymphocytes (TIL) and elevated Tconv/Treg and CD8+/Treg ratios. Furthermore, depletion of CD8+ T cells but not NK cells abrogated the therapeutic effect of DCVacc/VSV-GP. Taken together, the combination of VSV-GP and DC-based immunotherapy might represent a promising therapeutic option for the treatment of melanoma. Citation Format: Zoltan Banki, Iris Koske, Isabel Barnstorf, Christoph Tripp, Patrizia Stoitzner, Nikolaus Romani, Guido Wollmann, Janine Kimpel, Dorothee Holm-von Laer. Oncolytic virotherapy combination with DC-based immunotherapy for the treatment of melanoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A038.