Allogeneic whole-cell vaccine: a phase I/II study in men with hormone-refractory prostate cancer

BJU Int. 2002 Jan;89(1):19-26.

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.

Patients and 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.

Conclusion: 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.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bacterial Vaccines / administration & dosage*
  • Bacterial Vaccines / adverse effects
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • Cell Division
  • Cohort Studies
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunotherapy / adverse effects
  • Immunotherapy / methods*
  • Male
  • Middle Aged
  • Mycobacterium / immunology*
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • T-Lymphocytes / immunology
  • Transplantation, Homologous
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects

Substances

  • Bacterial Vaccines
  • Cancer Vaccines
  • Cytokines
  • Vaccines, Attenuated
  • Prostate-Specific Antigen