title: Treatment of biochemical recurrence of prostate cancer with granulocyte-macrophage colony-stimulating factor secreting, allogeneic, cellular immunotherapy.
abstract: OBJECTIVE
  This phase I-II study evaluated the safety, clinical activity and immunogenicity of an immunotherapy developed from human prostate cancer cell lines (PC-3 and LNCaP) modified to secrete granulocyte-macrophage colony-stimulating factor.
  
  
  METHODS
  Patients with noncastrate prostate cancer (19) with biochemical (prostate specific antigen) recurrence following prostatectomy or radiation therapy and no radiological evidence of metastasis were enrolled in the study. Patients were injected with an initial dose of 5 x 10(8) cells followed by 12 biweekly administrations of 1 x 10(8) cells. The adverse event profile, prostate specific antigen response, changes in prostate specific antigen kinetics and immunogenicity were assessed.
  
  
  RESULTS
  Immunotherapy was well tolerated with no serious treatment related adverse events and no autoimmune reactions. A negative deflection in prostate specific antigen slope was observed in 84% of patients after treatment with a significant increase in median prostate specific antigen doubling time from 28.7 weeks before treatment to 57.1 weeks after treatment (p = 0.0095). Median time to prostate specific antigen progression was 9.7 months. Immunoblot analysis of patient serum demonstrated new or enhanced production of PC-3 or LNCaP reactive antibodies in 15 of 19 (79%) patients after immunotherapy. Induction of antibody responses reactive against PC-3 in general, and to the PC-3 associated filamin-B protein specifically, were positively associated with treatment associated changes in prostate specific antigen kinetics.
  
  
  CONCLUSIONS
  Granulocyte-macrophage colony-stimulating factor secreting cellular immunotherapy has a favorable toxicity profile with signals of clinical and immunological activity against hormone naïve prostate cancer. An association between immune response and prostate specific antigen changes was observed. Phase 3 trials in patients with advanced, metastatic, hormone refractory prostate cancer are under way.
authors.affiliation: Earle A. Chiles Research Institute, Providence Portland Medical Center, Portland, Oregon 97213, USA. walter.urba@providence.or
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Urba
authors.forename: John
authors.initials: J
authors.lastname: Nemunaitis
authors.forename: Fray
authors.initials: F
authors.lastname: Marshall
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Hege
authors.forename: Jia
authors.initials: J
authors.lastname: Ma
authors.forename: Minh
authors.initials: M
authors.lastname: Nguyen
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D011336:Probability; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D020266:Radiotherapy, Conformal / Q000379:methods; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D019496:Cancer Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen