Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study
Background and aims
Dendritic cell (DC)-based vaccination can induce antitumor T cell responses in vivo. This clinical pilot study examined feasibility and outcome of DC-based tumor vaccination for patients with advanced pancreatic adenocarcinoma.
Tumor lysate of patients with pancreatic carcinoma was generated by repeated freeze–thaw cycles of surgically obtained tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were generated from peripheral blood mononuclear cells (PBMC), loaded with autologous tumor lysate, stimulated with TNF-α and PGE2 and injected intradermally. All patients received concomitant chemotherapy with gemcitabine. Disease response was the primary endpoint. Individual immunological responses to DC vaccination were analyzed by T cell-based immunoassays using pre- and post-vaccination samples of non-adherent PBMC.
Twelve patients received DC vaccination and concomitant chemotherapy. One patient developed a partial remission, and two patients remained in stable disease. Median survival was 10.5 months. No severe side effects were observed. Tumor-reactive T cells could be detected prior to vaccination. DC vaccination increased the frequency of tumor-reactive cells in all patients tested; however, the degree of this increase varied. To quantify the presence of tumor-reactive T cells, stimulatory indices (SI) were calculated as the ratio of proliferation-inducing capacity of lysate-loaded versus -unloaded DC. The patient with longest overall survival of 56 months had a high SI of 6.49, indicating that the presence of a pre-vaccination antitumor T cell response might be associated with prolonged survival. Five patients survived 1 year or more.
DC-based vaccination can stimulate an antitumoral T cell response in patients with advanced or recurrent pancreatic carcinoma receiving concomitant gemcitabine treatment.
KeywordsImmunotherapy Pancreatic cancer Dendritic cell Vaccination
Died of other causes
Dead of disease
Keyhole limpet hemocyanin
Peripheral blood mononuclear cells
Phorbol 12-myristate 13-acetate
Transforming growth factor-β
This work was supported by grants from the Gravenhorst Stiftung (M.D.), the Förderprogramm für Forschung und Lehre (FöFoLe) of the University of Munich (C.B.), the Deutsche Forschungsgemeinschaft (Ba 3824/1-1 to C.B. and Graduiertenkolleg 1202 to M.S., S.E.), and the Deutsche Krebshilfe (M.S.). This work is part of the doctoral thesis of S.S. at the University of Munich.
Conflict of interest
All authors declare that no conflicts of interest exist.
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