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Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model
  1. Christian Alexander Bauer (christian.bauer{at}med.uni-muenchen.de)
  1. Medizinische Klinik Innenstadt, University of Munich, Germany
    1. Franz Bauernfeind
    1. Medizinische Klinik Innenstadt, University of Munich, Germany
      1. Alexander Sterzik
      1. Medizinische Klinik Innenstadt, University of Munich, Germany
        1. Martin Orban
        1. Medizinische Klinik Innenstadt, University of Munich, Germany
          1. Max Schnurr
          1. Medizinische Klinik Innenstadt, University of Munich, Germany
            1. Hans Anton Lehr
            1. Institut Universitaire de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
              1. Stefan Endres
              1. Medizinische Klinik Innenstadt, University of Munich, Germany
                1. Andreas Eigler
                1. Medizinische Klinik Innenstadt, University of Munich, Germany
                  1. Marc Dauer (marc.dauer{at}med.uni-muenchen.de)
                  1. Medizinische Klinik Innenstadt, University of Munich, Germany

                    Abstract

                    Background: Tumor-specific cytotoxic T lymphocytes (CTL) can be activated in vivo by vaccination with dendritic cells (DC). However, clinical responses to DC-based vaccination have only been observed in a minority of patients with solid cancer. Combination with other treatment modalities such as chemotherapy may overcome immunoresistance of cancer cells. We have previously shown that gemcitabine sensitizes human pancreatic carcinoma cells against CTL- mediated lysis. Here, we used a murine pancreatic carcinoma model to investigate whether combination with gemcitabine increases therapeutic efficacy of DC-based vaccination.

                    Methods: Bone marrow-derived DC from C57BL/6 mice were loaded with UV-irradiated, syngeneic Panc02 carcinoma cells and were administered subcutaneously. For prophylactic vaccination, mice were vaccinated three times in weekly intervals prior to tumor challenge with Panc02 cells. Therapeutic vaccination was started when tumors formed a palpable nodule. Gemcitabine was administered intraperitoneally twice weekly.

                    Results: Prophylactic DC-based vaccination completely prevented subcutaneous and orthotopic tumor development and induced immunological memory as well as tumor antigen-specific CTL. In the subcutaneous tumor model, therapeutic DC-based vaccination was equally effective as gemcitabine (14 % vs. 17 % survival at day 58 after tumor challenge; controls: 0 %). Combination of the two strategies significantly increased survival of tumor-bearing mice (50 % at day 58 after tumor challenge). DC-based vaccination also prevented death from pulmonary metastatization after i.v.-injection of Panc02 cells.

                    Conclusion: DC-based immunotherapy may not only be successfully combined with gemcitabine for the treatment of advanced pancreatic carcinoma, but may also be effective in preventing local recurrence or metastatization in tumor-free patients.

                    • chemotherapy
                    • dendritic cells
                    • gemcitabine
                    • pancreatic carcinoma
                    • vaccination

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