Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24+ prostate cancer patients

Br J Cancer. 2004 Jul 19;91(2):287-96. doi: 10.1038/sj.bjc.6601960.

Abstract

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology
  • Case-Control Studies
  • Cell Survival / immunology
  • HLA-A Antigens / immunology*
  • HLA-A24 Antigen
  • Humans
  • Immunoglobulin G / immunology
  • Interferon-gamma / metabolism
  • Male
  • Parathyroid Hormone-Related Protein / immunology*
  • Peptide Fragments / immunology*
  • Prostate
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Cells, Cultured

Substances

  • HLA-A Antigens
  • HLA-A24 Antigen
  • Immunoglobulin G
  • Parathyroid Hormone-Related Protein
  • Peptide Fragments
  • Interferon-gamma