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Merck
CN
  • 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.

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.

Cancer immunology, immunotherapy : CII (2014-01-05)
Christian Bauer, Alexander Sterzik, Franz Bauernfeind, Peter Duewell, Claudius Conrad, Rosemarie Kiefl, Stefan Endres, Andreas Eigler, Max Schnurr, Marc Dauer
摘要

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. Subcutaneous or orthotopic pancreatic tumors were induced in C57BL/6 mice using Panc02 cells expressing the model antigen OVA. 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 tumor-reactive T-cells in peripheral blood, in vivo cytotoxicity assays revealed that cytotoxic T-cell (CTL)-mediated killing was preserved. In vitro assays revealed sensitization of tumor 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 tumor-reactive T-cells in peripheral blood may thus not predict vaccination success in the setting of concomitant chemotherapy.

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Sigma-Aldrich
白蛋白 来源于鸡蛋白, lyophilized powder, ≥98% (agarose gel electrophoresis)
Sigma-Aldrich
白蛋白 来源于鸡蛋白, lyophilized powder, ≥98% (agarose gel electrophoresis)
Sigma-Aldrich
白蛋白 来源于鸡蛋白, powder, 62-88% (agarose gel electrophoresis)
Sigma-Aldrich
白蛋白 来源于鸡蛋白, lyophilized powder
Sigma-Aldrich
白蛋白 来源于鸡蛋白, lyophilized powder, ≥90% (agarose gel electrophoresis)
Supelco
白蛋白 来源于鸡蛋白, For use as a marker in SDS-PAGE