14102 Background: Vaccination trials in the experimental and in the clinical setting have shown that it is possible to use dendritic cells (DC) to induce a specific antitumoral immune response. In this study, a protocol for the treatment of patients with metastasised pancreatic carcinoma with autologous, tumor-lysate pulsed dendritic cells was established. Methods: Patients with strong suspicion of pancreatic carcinoma receiving abdominal surgery are recruited to the study. Tumor-lysate is derived by freeze-taw-cycles from surgically derived tissue specimens. After recurrence of histologically verified pancreatic carcinoma or in a primarily palliative situation, patients are eligible for DC vaccination. DC are derived from PBMC according to a six-day protocol, loaded with tumor lysate and stimulated with TNF-alpha and PgE2. DC are applicated intracutaneously into the groin region three times in twice weekly cycles, then in monthly cycles. Immune response is controlled by DTH skin testing. Samples of non adherent cells are frozen for future MLR and ELISPOT assays. Main study end point is partial or complete remission four months after the start of vaccination. Alternative end points are adverse effects, quality of life, one-year survival and immuno-monitoring. Results: Tumor material of 49 patients has been worked up to tumor lysate and stored for future vaccinations. Four patients have received dendritic cell vaccination. Two of these patients have received their four months staging CT. In one case local disease was stable. The other patient showed progressive disease. A more pronounced proliferation of specific T cells compared to the control setting could be demonstrated by MLR assay. Discussion: A protocol for vaccination with tumor lysate pulsed dendritic cells of patients with pancreatic carcinoma has been established. Four patients have been vaccinated with dendritic cells according to a phase II study protocol. Vaccination was tolerated well. Because of a severe adverse reaction after the beginning of gemcitabine therapy, vaccination had to be omitted intercurrently with this patient. Results of most immuno monitoring assays are pending. One patient receiving DC vaccination therapy showed stable local disease. No significant financial relationships to disclose.
A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma
