Photoimmunotherapy of melanoma via combination of hypericin- Photodynamic therapy and in vivo stimulation of dendritic cells by PNGVL3-HFLEX Plasmid DNA

Abstract

Recently, combination treatment of photodynamic therapy (PDT) with dendritic cell (DC)-based immunotherapy also termed photoimmunotherapy has been shown to be an effective anti-tumor treatment. In these studies, the DCs were expanded in vitro and primed in vivo via intratumoral injection of DCs. In the present study, the anti-tumor effectiveness of a novel anti-cancer treatment via photoimmunotherapy uitilizing the combination of hypericin (HY)-PDT and in vivo stimulation of DCs via pNGVL3-hFlex plasmid DNA was investigated in murine B16 melanoma. The anti-tumor effectiveness of PDT alone, photoimmunotherapy and control were compared in vivo in various murine models including a primary tumor model, distant established tumor (metastatic) model and when exposed to a second tumor challenge (tumor vaccine model). Photoimmunotherapy was superior to both control and PDT alone in suppressing tumor growth on a small established contralateral tumor and when exposed to a second tumor challenge. However, it was not effective in suppressing the growth of a large established contralateral tumor. Photoimmunotherapy was also not superior to PDT alone in controlling the primary tumor. In conclusion, photoimmunotherapy using HY-based PDT and in vivo DC expansion by pNGVL3-Flex plasmid DNA is a novel anti-cancer modality which results in an effective systemic tumor specific anti-tumor immune response which suppresses tumor growth at distant sites.