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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
Journal for ImmunoTherapy of Cancer volume 2, Article number: P1 (2014)
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.
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.
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.
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Cite this article
Bauer, C., Sterzik, A., Bauernfeind, F. et al. 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. j. immunotherapy cancer 2, P1 (2014). https://doi.org/10.1186/2051-1426-2-S2-P1
- Pancreatic Carcinoma
- Panc02 Cell
- Dendritic Cell Vaccination
- Dendritic Cell Migration