Immunological evaluation of individualized peptide vaccination with a low dose of estramustine for HLA-A24+ HRPC patients

Prostate. 2005 Apr 1;63(1):1-12. doi: 10.1002/pros.20157.

Abstract

Background: The safety, toxicity, and immunological response of individualized peptide vaccination or human leukocyte antigen (HLA)-A24+ hormone refractory prostate cancer (HRPC) patients in combination with a low dose of estramustine were evaluated.

Methods: Sixteen patients with HLA-A24+ HRPC were enrolled in the phase I/II study. Conducted immune monitorings for those patients were peptide-specific cytotoxic T lymphocyte (CTL) precursor analysis by interferon-gamma production and peptide-reactive immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay. Clinical responses and quality of life (QOL) outcomes using a self-reported patient questionnaire were also evaluated.

Results: Vaccinations were well tolerated, but all patients developed grade 1 or 2 local redness and swelling at the injection site. There was no significant immunosuppression in most cases when the peptide and a half dose (280 mg/day) of estramustine were administrated. Augmentation of peptide-specific CTL precursors or peptide-specific IgG was observed in 10 of 14 or 7 of 14 patients at 12 weeks (peptide vaccination alone), and in 6 of 8 or 10 of 12 patients at 24 weeks (during the combination therapy), respectively. All 13 patients treated, with the combination therapy, showed a decrease of serum prostate-specific antigen (PSA) level from the baseline, including six patients with a serum PSA level decrease of >or=50%. QOL outcomes were not deteriorated during the treatment.

Conclusion: These results might encourage the further evaluation of the combination of peptide vaccination and a low dose of estramustine phosphate for HLA-A24+ HRPC patients.

Publication types

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

MeSH terms

  • Aged
  • Antineoplastic Agents, Alkylating / administration & dosage*
  • Combined Modality Therapy
  • Estramustine / administration & dosage*
  • Follow-Up Studies
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Immunotherapy
  • Male
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / mortality
  • Quality of Life
  • Treatment Outcome
  • Vaccines, Subunit / administration & dosage*

Substances

  • Antineoplastic Agents, Alkylating
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Vaccines, Subunit
  • Estramustine