Induction of cellular and humoral immune responses to tumor cells and peptides in HLA-A24 positive hormone-refractory prostate cancer patients by peptide vaccination

Prostate. 2003 Sep 15;57(1):80-92. doi: 10.1002/pros.10276.

Abstract

Background: To assess the safety and immune response of a peptide-based immunotherapy for patients with hormone-refractory prostate cancer, a phase I clinical trial was conducted.

Methods: This study first investigated whether cytotoxic T-lymphocyte (CTL) precursors reacting to peptide with vaccine candidates (14 peptides for HLA-A24 positive patients) were detectable in the pre-vaccination peripheral blood mononuclear cells (PBMCs) of ten patients with hormone-refractory prostate cancer. Patients were then vaccinated subcutaneously with only those peptides to which pre-vaccination PBMCs reacted (CTL precursor-oriented peptide vaccine) for up to four kinds of peptides.

Results: Overall vaccinations were generally well tolerated, but most patients (nine of ten) developed grade 1 local redness and swelling at the injection site. Increased CTL response to both peptides and cancer cells were observed in four of ten patients. Anti-peptide IgG antibodies were also detected in post-vaccination sera of seven of ten patients. One patient achieved a partial response with an 89% decrease in PSA. Stable disease was demonstrated in five of ten patients (50%) for the median duration of 2 months (range, 2-5 months). There were no objective responses of measurable lesions.

Conclusions: Increase in cellular and humoral immune responses, and decrease in PSA level in some patients support further development of peptide-based immunotherapy for hormone refractory prostate cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma / chemistry
  • Adenocarcinoma / immunology*
  • Adenocarcinoma / therapy*
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / analysis
  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / adverse effects
  • DNA-Binding Proteins / analysis
  • HLA-A Antigens / analysis
  • HLA-A24 Antigen
  • Humans
  • Immunoglobulin G / blood
  • Immunotherapy
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / analysis
  • Male
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / therapy*
  • RNA-Binding Proteins / analysis
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • DNA-Binding Proteins
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Immunoglobulin G
  • Neoplasm Proteins
  • RNA-Binding Proteins
  • SART3 protein, human
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Prostate-Specific Antigen
  • DSE protein, human