Vaccination of hormone-refractory prostate cancer patients with peptide cocktail-loaded dendritic cells: results of a phase I clinical trial

Prostate. 2006 Jun 1;66(8):811-21. doi: 10.1002/pros.20404.

Abstract

Background: Immunotherapies might represent promising alternatives for the treatment of patients with hormone-refractory prostate cancer (HRPC). In a Phase I clinical trial, we evaluated a vaccination with dendritic cells (DCs) loaded with a cocktail consisting of HLA-A*0201-restricted peptides derived from five different prostate cancer-associated antigens [prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), survivin, prostein, transient receptor potential p8 (trp-p8)].

Methods: Eight HRPC patients received a total of four vaccinations every other week. Clinical and immunological responses were monitored by the determination of the serum PSA levels and by enzyme linked immunospot (ELISPOT) analyses, respectively.

Results: Apart from local skin reactions no side effects were noted. One patient displayed a partial response (PR; PSA decrease >50%) and three other patients showed stable PSA values or decelerated PSA increases. In ELISPOT analyses, three of four PSA responders also showed antigen-specific CD8+ T-cell activation against prostein, survivin, and PSMA.

Conclusions: The described protocol represents a safe and feasible concept for the induction of clinical and immunological responses. The application of a peptide cocktail-derived from different antigens as a novel treatment modality is supposed to allow for the genetic and biologic heterogeneity of PCa.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antigens, Surface / analysis
  • Antigens, Surface / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / administration & dosage
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology*
  • Drug Resistance, Neoplasm
  • Glutamate Carboxypeptidase II / analysis
  • Glutamate Carboxypeptidase II / immunology
  • HLA-A Antigens / chemistry
  • HLA-A Antigens / immunology
  • HLA-A Antigens / therapeutic use*
  • HLA-A2 Antigen
  • Humans
  • Immunoenzyme Techniques
  • Immunomagnetic Separation
  • Immunotherapy, Active
  • Inhibitor of Apoptosis Proteins
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / immunology
  • Microtubule-Associated Proteins / analysis
  • Microtubule-Associated Proteins / immunology
  • Middle Aged
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / immunology
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Survivin
  • TRPM Cation Channels / analysis
  • TRPM Cation Channels / immunology

Substances

  • Antigens, Surface
  • BIRC5 protein, human
  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Inhibitor of Apoptosis Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • TRPM Cation Channels
  • TRPM8 protein, human
  • prostein
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Prostate-Specific Antigen