Prostate-related antigen-derived new peptides having the capacity of inducing prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients

Oncol Rep. 2004 Sep;12(3):601-7.


Prostate-related antigens, including prostate-specific membrane antigen (PSMA) and prostatic acid phosphatase (PAP), can be targets in specific immunotherapy for prostate cancer. In this study, we attempted to newly identify epitope peptides from these 2 antigens, which are immunogenic in human histocompatibility leukocyte antigen (HLA)-A2+ prostate cancer patients. Twenty-nine peptides (PSMA with 15 and PAP with 14) were prepared based on the HLA-A2 binding motif. Based on our previous finding that antigenic peptides recognized by both cellular and humoral immune systems are useful for peptide-based immunotherapy, peptide candidates were screened first by their ability to be recognized by immunoglobulin G (IgG), and then by their ability to induce peptide-specific cytotoxic T lymphocytes (CTLs). As a result, PSMA441-450 and PAP112-120 peptides were found to be frequently recognized by IgG in plasma from prostate cancer patients. These 2 candidates effectively induced HLA-A2-restricted and prostate cancer-reactive CTLs in HLA-A2+ prostate cancer patients with several HLA-A2 subtypes. In addition, their cytotoxicity was mainly dependent on peptide-specific and CD8+ T cells. These results indicate that these PSMA441-450 and PAP112-120 peptides could be promising candidates for peptide-based immunotherapy for HLA-A2(+) prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Antigens, Surface / chemistry*
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes / chemistry
  • Glutamate Carboxypeptidase II / chemistry*
  • HLA-A2 Antigen / biosynthesis*
  • Humans
  • Immunoglobulin G / chemistry
  • Immunotherapy / methods*
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / metabolism*
  • Time Factors


  • Antigens, Surface
  • Epitopes
  • HLA-A2 Antigen
  • Immunoglobulin G
  • Peptides
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II