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Keywords:

  • prostate cancer;
  • PSCA;
  • cytotoxic T lymphocytes;
  • HLA-A24;
  • peptide;
  • antibody

Abstract

BACKGROUND

We attempted to identify prostate stem cell antigen (PSCA)-derived peptides immunogenic in HLA-A24+ prostate cancer patients.

METHODS

Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with each of three different PSCA-derived peptides, which were prepared based on the HLA-A24 binding motif, and their peptide-specific and HLA-A24-restricted anti-tumor responses were examined. Plasma levels of immunoglobulin G (IgG) against PSCA peptides were measured by enzyme-linked immunosorbent assay (ELISA).

RESULTS

Among three PSCA peptides, the PSCA 76–84 peptide most effectively induced peptide-specific cytotoxic T lymphocytes (CTLs) from PBMCs of HLA-A24+ prostate cancer patients. Cytotoxicity was dependent on peptide-specific and CD8+ T cells. The PSCA 76–84 peptide-stimulated PBMCs showed a significant level of cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. IgG reactive to the PSCA 76–84 peptide was detected in half of patients.

CONCLUSIONS

The PSCA 76–84 peptide should be considered for use in clinical trials of immunotherapy for HLA-A24+ patients. © 2004 Wiley-Liss, Inc.