title: Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  DC-based vaccination can stimulate an antitumoral T cell response in patients with advanced or recurrent pancreatic carcinoma receiving concomitant gemcitabine treatment.
authors.affiliation: Medizinische Klinik Innenstadt, University of Munich, München, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bauer
authors.forename: Marc
authors.initials: M
authors.lastname: Dauer
authors.forename: Samira
authors.initials: S
authors.lastname: Saraj
authors.forename: Maximilian
authors.initials: M
authors.lastname: Schnurr
authors.forename: Franz
authors.initials: F
authors.lastname: Bauernfeind
authors.forename: Alexander
authors.initials: A
authors.lastname: Sterzik
authors.forename: Jana
authors.initials: J
authors.lastname: Junkmann
authors.forename: Veronika
authors.initials: V
authors.lastname: Jakl
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kiefl
authors.forename: Fuat
authors.initials: F
authors.lastname: Oduncu
authors.forename: Bertold
authors.initials: B
authors.lastname: Emmerich
authors.forename: Doris
authors.initials: D
authors.lastname: Mayr
authors.forename: Thomas
authors.initials: T
authors.lastname: Mussack
authors.forename: Christiane
authors.initials: C
authors.lastname: Bruns
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
authors.forename: Claudius
authors.initials: C
authors.lastname: Conrad
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Stefan
authors.initials: S
authors.lastname: Endres
authors.forename: Andreas
authors.initials: A
authors.lastname: Eigler
mesh_terms: D000328:Adult; D000368:Aged; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D019496:Cancer Vaccines; D002277:Carcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone