gms | German Medical Science

27. Deutscher Krebskongress

Deutsche Krebsgesellschaft e. V.

22. - 26.03.2006, Berlin

Immunomonitoring of the CapRI Trial: First Results

Meeting Abstract

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  • corresponding author presenting/speaker Angela Märten - Universitätsklinikum, Heidelberg, Deutschland
  • Dirk Jäger - NCT, Heidelberg
  • Markus Büchler - Universitätsklinikum, Heidelberg
  • Jan Schmidt - Universitätsklinikum, Heidelberg

27. Deutscher Krebskongress. Berlin, 22.-26.03.2006. Düsseldorf, Köln: German Medical Science; 2006. DocPO130

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Veröffentlicht: 20. März 2006

© 2006 Märten et al.
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In August 2004 we have started a phase III trial, where we compare combined chemoradiotherapy plus IFN-α (arm A) with 5-FU bolus infusion (arm B) in patients with pancreatic adenocarcinoma in the adjuvant setting. We hypothesize that IFN-α is the agent that turns a slightly effective treatment (radiochemotherapy) into a potent therapy. Hypothesizing that the main mechanism of IFN-α is via immuno-modulation, we perform a broad immunomonitoring. Blood samples from patients of both arms are drawn at several time-points for immunological studies. The panel includes immunophenotyping, detection of cytokine mRNA in lymphocytes, cytokine pattern, cellular cytotoxicity assays and immunohistochemical analysis of tumor samples. Currently, we have analyzed samples from 24 patients for cellular cytotoxicity, granzyme B secretion, cytokine levels and by FACS. Interestingly, we observed with regard to NK cell mediated cytotoxicity an increase in cytotoxicity for PBL against K562 cells from patients in arm A during treatment. Cytotoxicity increased from 13% before first administration of IFN-α to 45% after 24hrs, dropped then but remained increased during treatment. The mean cytotoxicity of about 20% at an effector to target cell ratio of 80:1 in arm B did not change. Specific granzyme B secretion was analyzed in ELISpot after MUC-1 and/or CA19.9 stimulation. Again, there was no change in arm B patient’s PBL and no specific secretion (compared with medium control). Arm A patients showed an increase in CA 19.9 and MUC-1 specific granzyme B secretion after the second IFN-α dosage. Furthermore, we analyzed serum levels of cytokines. Only with regard to IL-12 we observed elevated serum levels in group with peaks one day after IFN-α injection. FACS analysis of peripheral blood showed a significant increase in monocytes, peripheral dendritic cells, CD80, CD40 and IFN-αR expression on monocytes and effector memory T cells in arm A patients. Percentage of naïve lymphocytes decreased. The effects were most pronounced after the first administra-tion of IFN-α. To summarize, we observed so far an increase in NK and T cell cytotoxicity, IL-12 secretion and an activation of monocytes in group A patients with a peak one day after the first administration of IFN-α.