title: A lethally irradiated allogeneic granulocyte-macrophage colony stimulating factor-secreting tumor vaccine for pancreatic adenocarcinoma. A Phase II trial of safety, efficacy, and immune activation.
abstract: OBJECTIVE
  Surgical resection provides the only possibility of cure for pancreas cancer. A standard adjuvant approach has not been established. We tested the safety and efficacy of a granulocyte-macrophage colony-stimulating factor (GM-CSF)-based immunotherapy administered in patients with resected pancreatic adenocarcinoma.
  
  
  METHODS
  A single institution phase II study of 60 patients with resected pancreatic adenocarcinoma was performed. Each immunotherapy treatment consisted of a total of 5 × 108 GM-CSF-secreting cells distributed equally among 3 lymph node regions. The first immunotherapy treatment was administered 8 to 10 weeks after surgical resection. Subsequently, patients received 5-FU based chemoradiation. Patients who remained disease-free after completion of chemoradiotherapy received treatments 2 to 4, each 1 month apart. A fifth and final booster was administered 6 months after the fourth immunotherapy. The primary endpoint was disease free survival and secondary endpoints were overall survival and toxicity, and the induction of mesothelin specific T cell responses.
  
  
  RESULTS
  The median disease-free survival is 17.3 months (95% CI, 14.6-22.8) with median survival of 24.8 months (95% CI, 21.2-31.6). The administration of immunotherapy was well tolerated. In addition, the post-immunotherapy induction of mesothelin-specific CD8+ T cells in HLA-A1+ and HLA-A2+patients correlates with disease-free survival.
  
  
  CONCLUSIONS
  An immunotherapy approach integrated with chemoradiation is safe and demonstrates an overall survival that compares favorably with published data for resected pancreas cancer. These data suggest additional boost immunotherapies given at regular intervals beyond 1 year postsurgery should be tested in future studies, and provide the rationale for conducting a multicenter phase II study.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Lutz
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Yeo
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: Barbara
authors.initials: B
authors.lastname: Biedrzycki
authors.forename: Barry
authors.initials: B
authors.lastname: Kobrin
authors.forename: Joseph
authors.initials: J
authors.lastname: Herman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sugar
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Sara
authors.initials: S
authors.lastname: Solt
authors.forename: Beth
authors.initials: B
authors.lastname: Onners
authors.forename: Irena
authors.initials: I
authors.lastname: Tartakovsky
authors.forename: Miri
authors.initials: M
authors.lastname: Choi
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Peter B
authors.initials: PB
authors.lastname: Illei
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Ross A
authors.initials: RA
authors.lastname: Abrams
authors.forename: Dung
authors.initials: D
authors.lastname: Le
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaffee
authors.forename: Dan
authors.initials: D
authors.lastname: Laheru
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000528:radiation effects / Q000627:therapeutic use*; D021441:Carcinoma, Pancreatic Ductal / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007167:Immunotherapy; D008297:Male; D000090204:Mesothelin; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000090204:Mesothelin