Identification of Prostate-Specific G-protein Coupled Receptor as a Tumor Antigen Recognized by CD8(+) T Cells for Cancer Immunotherapy

PLoS One. 2012;7(9):e45756. doi: 10.1371/journal.pone.0045756. Epub 2012 Sep 20.

Abstract

Background: Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8(+) T cells in an HLA-A2 dependent manner.

Methodology/principal findings: Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2(+) healthy donors or HLA-A2(+) prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner.

Conclusions/significance: We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8(+) T cells, which, in turn, recognize HLA-A2(+) and PSGR(+) tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / immunology*
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / chemical synthesis
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • HLA Antigens / metabolism
  • Humans
  • Immunotherapy, Active
  • Interferon-gamma / metabolism
  • Male
  • Neoplasm Proteins / immunology*
  • Neoplasm Proteins / metabolism
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology*
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • Receptors, Odorant / immunology*
  • Receptors, Odorant / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism

Substances

  • Antigens, Neoplasm
  • Cancer Vaccines
  • HLA Antigens
  • Neoplasm Proteins
  • OR51E2 protein, human
  • Peptide Fragments
  • Receptors, Odorant
  • Interferon-gamma