Identification of an HLA-A*0201-restricted T-cell epitope derived from the prostate cancer-associated protein prostein

Br J Cancer. 2004 Mar 8;90(5):1034-40. doi: 10.1038/sj.bjc.6601642.

Abstract

The development of T-cell-based immunotherapies of cancer largely depends on the availability of tumour-associated antigens capable of eliciting tumour-directed cytotoxic T-cell responses. In prostate cancer, the number of antigens defined as suitable targets of cytotoxic T lymphocytes (CTLs) is still limited. Recently, prostein was identified as a transmembrane protein that is highly restricted to prostate tissues. In our study, prostein transcripts were found to be abundant in both malignant and nonmalignant prostate tissue samples. To identify immunogenic CD8+ T-cell epitopes, human leucocyte antigen-A(*)0201-binding peptides were selected from the amino-acid sequence of prostein and were used for the in vitro stimulation of CD8+ T lymphocytes. Specific CTLs were raised against the prostein-derived peptide CLAAGITYV that were capable of lysing prostate cancer cells, indicating that this peptide is naturally generated by tumour cells. Our data suggest that prostein is a suitable candidate to be included in a T-cell-based immunotherapy of prostate cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • CD8-Positive T-Lymphocytes / immunology*
  • Chromium / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • HLA-A Antigens / immunology*
  • HLA-A Antigens / metabolism
  • HLA-A2 Antigen
  • Humans
  • K562 Cells
  • Male
  • Membrane Proteins / immunology*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Peptide Fragments / immunology*
  • Peptide Fragments / metabolism
  • Prostate / immunology
  • Prostate / metabolism
  • Prostate-Specific Antigen / immunology
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • Membrane Proteins
  • Peptide Fragments
  • RNA, Messenger
  • prostein
  • Chromium
  • Prostate-Specific Antigen