title: Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation.
abstract: OBJECTIVE
  The combination of chemotherapy and immunotherapy has not been examined in patients with advanced pancreatic cancer. We conducted a study of two granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines (CG8020/CG2505) as immunotherapy administered alone or in sequence with cyclophosphamide in patients with advanced pancreatic cancer.
  
  
  METHODS
  This was an open-label study with two cohorts: cohort A, 30 patients administered a maximum of six doses of CG8020/CG2505 at 21-day intervals; and cohort B, 20 patients administered 250 mg/m(2) of cyclophosphamide i.v. 1 day before the same immunotherapy given as in cohort A. The primary objective was to evaluate safety and duration of immunity. Secondary objectives included time to disease progression and median overall survival.
  
  
  RESULTS
  The administration of CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity. Median survival values in cohort A and cohort B were 2.3 and 4.3 months, respectively. CD8(+) T-cell responses to HLA class I-restricted mesothelin epitopes were identified predominantly in patients treated with cyclophosphamide + CG8020/CG2505 immunotherapy.
  
  
  CONCLUSIONS
  Granulocyte macrophage colony-stimulating factor-secreting pancreatic cancer cell lines CG8020/CG2505 alone or in sequence with cyclophosphamide showed minimal treatment-related toxicity in patients with advanced pancreatic cancer. Also, mesothelin-specific T-cell responses were detected/enhanced in some patients treated with CG8020/CG2505 immunotherapy. In addition, cyclophosphamide-modulated immunotherapy resulted in median survival in a gemcitabine-resistant population similar to chemotherapy alone. These findings support additional investigation of cyclophosphamide with CG8020/CG2505 immunotherapy in patients with advanced pancreatic cancer.
authors.affiliation: Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, The Johns Hopkins University School of Public Health, Baltimore, Maryland 21231, USA. laherda@jhmi.edu
authors.forename: Dan
authors.initials: D
authors.lastname: Laheru
authors.forename: Eric
authors.initials: E
authors.lastname: Lutz
authors.forename: James
authors.initials: J
authors.lastname: Burke
authors.forename: Barbara
authors.initials: B
authors.lastname: Biedrzycki
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: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Dung
authors.initials: D
authors.lastname: Le
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Sugar
authors.forename: Kristen
authors.initials: K
authors.lastname: Hege
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jaffee
mesh_terms: D000230:Adenocarcinoma / Q000556:secondary / Q000628:therapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D010865:Pilot Projects; D015996:Survival Rate; D014018:Tissue Distribution
chemical_list: D018906:Antineoplastic Agents, Alkylating; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003520:Cyclophosphamide