Phase I clinical trial: T-cell therapy for prostate cancer using autologous dendritic cells pulsed with HLA-A0201-specific peptides from prostate-specific membrane antigen

Prostate. 1996 Dec;29(6):371-80. doi: 10.1002/(SICI)1097-0045(199612)29:6<371::AID-PROS5>3.0.CO;2-B.

Abstract

Background: Conventional treatment for metastatic prostate cancer have failed to demonstrate curative potential in all patients. Investigations involving the role of T-cell immunity in the clearance of neoplastic cells are now available. Development of T-cell immunotherapy may give a new approach to the treatment of advanced metastatic prostate cancer.

Methods: A phase I clinical trial assessing the administration of autologous dendritic cells (DC) pulsed with HLA-A0201-specific prostate-specific membrane antigen (PSMA) peptides were conducted. Participants were divided into five groups receiving four or five infusions of peptides alone (PSM-P1 or PSM-P2; groups 1 and 2, respectively), autologous DC (group 3), or DC pulsed with PSM-P1 or P2 (groups 4 and 5, respectively).

Results: No significant toxicity was observed in all five groups. Cellular response against PSM-P1 and -P2 was observed in HLA-A2+ patients infused with DC pulsed with PSM-P1 or -P2 (groups 4 and 5), respectively. An average decrease in PSA was detected only in group 5. Seven partial responders were identified based on NPCP criteria + PSA.

Conclusions: Infusions of test substances were well tolerated by all study participants. Detection of cellular response and decrease in PSA level in some patients who received DC pulsed with PSM-P2 indicate this method's potential in prostate cancer therapy.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dendritic Cells / chemistry*
  • Dendritic Cells / cytology
  • Dendritic Cells / physiology*
  • HLA-A Antigens / analysis*
  • HLA-A Antigens / immunology
  • Humans
  • Hypotension / epidemiology
  • Hypotension / physiopathology
  • Immunohistochemistry
  • Incidence
  • Interferon-alpha / blood
  • Male
  • Neoplasm Staging
  • Prostate-Specific Antigen / analysis*
  • Prostate-Specific Antigen / chemistry
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / therapy*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / physiology*
  • Tumor Necrosis Factor-alpha / analysis

Substances

  • HLA-A Antigens
  • Interferon-alpha
  • Tumor Necrosis Factor-alpha
  • Prostate-Specific Antigen