Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study

• Published in: Cancer Immunology, Immunotherapy Vol. 60; no. 8; pp. 1097 - 1107
• Main Authors: Bauer, Christian, Dauer, Marc, Saraj, Samira, Schnurr, Maximilian, Bauernfeind, Franz, Sterzik, Alexander, Junkmann, Jana, Jakl, Veronika, Kiefl, Rosemarie, Oduncu, Fuat, Emmerich, Bertold, Mayr, Doris, Mussack, Thomas, Bruns, Christiane, Rüttinger, Dominik, Conrad, Claudius, Jauch, Karl-Walter, Endres, Stefan, Eigler, Andreas
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.08.2011; Springer; Springer Nature B.V
• Subjects: Adult; Aged; Antigen Presentation; Antigens; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic agents; Biological and medical sciences; Cancer Research; Cancer Vaccines; Carcinoma - immunology; Carcinoma - pathology; Carcinoma - therapy; Chemotherapy; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - pathology; Dendritic Cells - transplantation; Dinoprostone - immunology; Dinoprostone - metabolism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Growth factors; Hospitals; Humans; Immunology; Immunotherapy; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Lymphocytes; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; Oncology; Original; Original Article; Pancreatic cancer; Pancreatic Neoplasms - immunology; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Patients; Pharmacology. Drug treatments; Pilot Projects; Treatment Outcome; Tumor Necrosis Factor-alpha - immunology; Tumor Necrosis Factor-alpha - metabolism; Tumors; Germany; Dendritic cell; Immunotherapy; Pancreatic cancer; Vaccination; Human; Patient; Malignant tumor; Prevention; Treatment; Antigen presenting cell; Pancreas cancer; Digestive diseases; Advanced stage; Cancer; Pancreatic disease; Pancreas carcinoma
• ISSN: 0340-7004; 1432-0851
• DOI: 10.1007/s00262-011-1023-5

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. Methods 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 PGE 2 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. Results 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. Conclusion DC-based vaccination can stimulate an antitumoral T cell response in patients with advanced or recurrent pancreatic carcinoma receiving concomitant gemcitabine treatment.