Identification of new prostate stem cell antigen-derived peptides immunogenic in HLA-A2(+) patients with hormone-refractory prostate cancer.

Abstract

Prostate cancer refractory to hormonal manipulation requires new treatment modalities. In the present study we attempted to identify prostate stem cell antigen (PSCA)-derived peptides immunogenic in HLA-A2+ prostate cancer patients in order to develop peptide-based immunotherapy against hormone-refractory prostate cancer (HRPC). Eleven different PSCA-derived peptides, which were prepared based on the HLA-A2 binding motif, were examined to determine whether they would be recognized by cellular and humoral immune responses in 12 HLA-A2+ patients (11 with HRPC and 1 with non-HRPC). Among the PSCA-derived peptides, PSCA 7-15 and PSCA 21-30 peptides effectively induced HLA-A2-restricted peptide-specific and tumor-reactive cytotoxic T lymphocytes (CTLs) from peripheral blood mononuclear cells (PBMCs) of HLA-A2+ patients. The PSCA 21-30 peptide was capable of inducing peptide-specific CTLs in both cancer patients and healthy donors, whereas the PSCA 7-15 peptide was immunogenic in only cancer patients. Immunoglobulin G (IgG) reactive to the PSCA 21-30 peptide was detected in plasma of most patients and healthy donors, whereas IgG reactive to PSCA 7-15 was undetectable in all cases. These results indicate that the former peptide elicits both cellular and humoral immune responses in both patients and healthy donors, whereas the latter elicits only cellular responses in patients. These two PSCA peptides should be considered for use in clinical trials of immunotherapy for HLA-A2+ HRPC patients.