title: Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation.
abstract: OBJECTIVE
  Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas.
  
  
  METHODS
  Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally.
  
  
  RESULTS
  No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received >or= 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis.
  
  
  CONCLUSIONS
  Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.
authors.affiliation: Department of Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. ejaffee@jhmi.edu
authors.forename: E M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: R H
authors.initials: RH
authors.lastname: Hruban
authors.forename: B
authors.initials: B
authors.lastname: Biedrzycki
authors.forename: D
authors.initials: D
authors.lastname: Laheru
authors.forename: K
authors.initials: K
authors.lastname: Schepers
authors.forename: P R
authors.initials: PR
authors.lastname: Sauter
authors.forename: M
authors.initials: M
authors.lastname: Goemann
authors.forename: J
authors.initials: J
authors.lastname: Coleman
authors.forename: L
authors.initials: L
authors.lastname: Grochow
authors.forename: R C
authors.initials: RC
authors.lastname: Donehower
authors.forename: K D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: S
authors.initials: S
authors.lastname: O'Reilly
authors.forename: R A
authors.initials: RA
authors.lastname: Abrams
authors.forename: D M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: J L
authors.initials: JL
authors.lastname: Cameron
authors.forename: C J
authors.initials: CJ
authors.lastname: Yeo
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000368:Aged; D019496:Cancer Vaccines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003257:Consumer Product Safety; D018572:Disease-Free Survival; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor