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  • P10. Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8+ T cell and B cell responses but improves clinical efficacy in a murine pancreatic carcinoma model

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Poster Presentation
P10. Concomitant gemcitabine therapy negatively affects DC vaccine-induced CD8+ T cell and B cell responses but improves clinical efficacy in a murine pancreatic carcinoma model
  1. C Bauer1,
  2. A Sterzik1,
  3. F Bauernfeind1,
  4. P Duewell2,
  5. C Conrad3,
  6. R Kiefl1,
  7. S Endres2,
  8. A Eigler4,
  9. M Schnurr1 and
  10. M Dauer5
  1. Aff1 Medizinische Klinik und Poliklinik IV LMU MunichSection of Gastroenterology Munich Germany
  2. Aff2 grid.5252.0000000041936973XDivision of Clinical Pharmacology LMU Munich Munich Germany
  3. Aff3 grid.32224.350000 0004 0386 9924Massachusetts General Hospital Harvard UniversityDepartment of Surgery Boston MA USA
  4. Aff4 Klinikum Dritter OrdenDepartment of Clinical Medicine I Munich Germany
  5. Aff5 Kliniken St. ElisabethDepartment of Medicine II Neuburg/Donau Germany

https://doi.org/10.1186/2051-1426-2-S2-P1

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    Meeting abstracts

    Background

    Multiple studies have shown that dendritic cell (DC)-based vaccines can induce antitumor immunity. Previously, we reported that gemcitabine enhances the efficacy of DC vaccination in a mouse model of pancreatic carcinoma. The present study aimed at investigating the influence of gemcitabine on vaccine-induced anti-tumoral immune responses in a syngeneic pancreatic cancer model.

    Material and methods

    Subcutaneous or orthotopic pancreatic tumours were induced in C57BL/6 mice using Panc02 cells expressing the model antigen OVA (PancOVA). Bone marrow-derived DC were loaded with soluble OVA protein (OVA-DC). Animals received gemcitabine twice weekly. OVA-specific CD8+ T cells and antibody titers were monitored by FACS analysis and ELISA, respectively.

    Results

    Gemcitabine enhanced clinical efficacy of the OVA-DC vaccine. Interestingly, gemcitabine significantly suppressed the vaccine-induced frequency of antigen-specific CD8+ T cells and antibody titers. DC migration to draining lymph nodes and antigen cross-presentation were unaffected. Despite reduced numbers of tumour-reactive T cells in peripheral blood, in vivo cytotoxicity assays revealed that CTL-mediated killing was preserved. In vitro assays revealed sensitization of tumour cells to CTL-mediated lysis by gemcitabine. In addition, gemcitabine facilitated recruitment of CD8+ T cells into tumors in DC-vaccinated mice. T and B cell suppression by gemcitabine could be avoided by starting chemotherapy after two cycles of DC vaccination.

    Conclusions

    Gemcitabine enhances therapeutic efficacy of DC vaccination despite its negative influence on vaccine-induced T cell proliferation. Quantitative analysis of tumour-reactive T cells in peripheral blood may thus not predict vaccination success in the setting of concomitant chemotherapy.