title: Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer.
abstract: OBJECTIVE
  To establish the safety and toxicity of an allogeneic human tumour cell vaccine in patients with hormone-refractory prostate cancer, and to determine any biochemical, immunological or clinical response to vaccination.
  
  
  METHODS
  Sixty patients with hormone-refractory prostate cancer were recruited and randomly allocated into four equal groups. Three cell lines (from a bank of four) were administered initially every 2 weeks and then monthly, in conjunction with the immunostimulant Mycobacterium vaccae (SRL-172), each group receiving a different combination of the four cell lines. The patients' serum prostate-specific antigen (PSA) levels were monitored regularly, and the immune response to the vaccine measured using nonspecific intracellular cytokines and specific humoral and cell-mediated assays.
  
  
  RESULTS
  The vaccine was safe and well tolerated with no major side-effects. Whilst several patients had a decline in PSA from the entry level, there was no significant decrease that could be attributed solely to the vaccine. However, the immunological data were more encouraging, with several patients from each arm of the trial having an increase in cytokine production, increases in specific antibodies and evidence of T-cell proliferation in response to the vaccinations.
  
  
  CONCLUSIONS
  The failure of the vaccine to produce a PSA response in the patients in the trial is not surprising considering the stage of the disease. The high PSA levels on entry indicate that the burden of disease was probably high and thus this was an extremely challenging group of patients in which to try and elicit a response through immunotherapy. However, the immunological evidence of a response to the vaccine was encouraging and suggests that further exploration of immunotherapy in less advanced disease may yield more encouraging clinical responses.
authors.affiliation: Division of Oncology, St George's Hospital Medical School, London, UK. joneaton@cwcom.net
authors.forename: J D
authors.initials: JD
authors.lastname: Eaton
authors.forename: M J A
authors.initials: MJ
authors.lastname: Perry
authors.forename: S
authors.initials: S
authors.lastname: Nicholson
authors.forename: M
authors.initials: M
authors.lastname: Guckian
authors.forename: N
authors.initials: N
authors.lastname: Russell
authors.forename: M
authors.initials: M
authors.lastname: Whelan
authors.forename: R S
authors.initials: RS
authors.lastname: Kirby
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D002455:Cell Division; D015331:Cohort Studies; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014184:Transplantation, Homologous; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D016207:Cytokines; D014613:Vaccines, Attenuated; D017430:Prostate-Specific Antigen