Immunological and clinical response after vaccination therapy of pancreatic carcinoma patients with autologous, tumor-lysate pulsed dendritic cells: Results of a phase II-study

Abstract

4579 Background: Multiple studies in the experimental and in the clinical setting have shown that vaccine therapy using dendritic cells can induce antitumor immunity. Here, we report about the results of a phase II-study using autologous, tumor-lysate pulsed dendritic cells for the treatment of patients with advanced pancreatic carcinoma. Methods: Pancreatic carcinoma patients receiving abdominal surgery were included into to the study protocol. Tumor-lysate was derived by freeze-taw-cycles from surgically derived tissue specimens. Patients were eligible for DC vaccination after recurrence of pancreatic carcinoma or in a primarily palliative situation. DC were derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-a and PgE2. DC were applicated intracutaneously into the groin region every other week for three cycles, then monthly. All patients received standard chemotherapy with gemcitabine concomitantly. Immune response was controlled by DTH skin testing. Samples of non adherent cells were frozen for MLR and ELISPOT assays to monitor immune response ex vivo. Main study end point was partial or complete remission. Results: Ten patients have received dendritic cell vaccination so far. Of these, one patient developed a partial remission after a four-months course of vaccination therapy. Another patient showed stable disease after having received five vaccinations. Both patients showed immunological response. The patient with stable disease had a mean of 56 IFN-γ positive spots per 50E3 DC-stimulated non adherent cells prior to vaccination. After vaccination, this number increased to 191 spots per 50E3 cells (negative control: 5; positive control: 315). Both patients are alive 13 and 7 months after the start of vaccination therapy, respectively. Conclusions: Vaccination therapy with dendritic cells can be of clinical benefit in the setting of advanced pancreatic carcinoma. Clinical responses were associated with the induction of a stable immunological response. No significant financial relationships to disclose.

Systemic therapy for metastatic pancreatic adenocarcinoma

“…Virulizin combined with gemcitabine did not improve survival in a randomized phase III study [Wright et al 2006]. Other immune agents in trial include the vaccine, panvac-VF G17DT, an immune stimulant that raises antibodies to growth factor gastrin-17 called immunogen, a vaccination therapy using degraded dendritic cells [Bauer et al 2007], and a peptide vaccine matched to circulating IgG antibodies and cytotoxic T cells [Yanagimoto et al 2006].…”