Identification of a prostate‐specific membrane antigen‐derived peptide capable of eliciting both cellular and humoral immune responses in HLA‐A24+ prostate cancer patients

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Abstract
We tried to identify prostate‐specific membrane antigen (PSMA)‐derived peptides capable of eliciting both cellular and humoral immune responses in peripheral blood mononuclear cells (PBMCs) and plasma of HLA‐A24+ prostate cancer patients, respectively. For cellular response, peptide‐specific and prostate cancer‐reactive responses of in vitro‐stimulated PBMCs were examined with regard to interferon (IFN)‐γ production and cytotoxicity against both a parental HLA‐A24− prostate cancer cell line (PC‐93) and an HLA‐A24‐expressing transfectant cell line (PC93‐A24). For humoral response, patients’ plasma was tested for reactivity to the peptides by means of an enzyme‐linked immunosorbent assay (ELISA). Among 13 PSMA peptides, PSMA 624–632 peptide induced peptide‐specific and tumor‐reactive cytotoxic T lymphocytes (CTLs) most effectively. The PSMA 624–632 peptide‐stimulated PBMCs from either healthy donors or prostate cancer patients produced a significant level of IFN‐γ in response to prostate cancer cells in an HLA‐A24‐restricted manner, and also showed a higher level of cytotoxicity against PC93‐A24 than against PC93. Antibodies to the PSMA 624–632 peptide, but not to any others, were detected in prostate cancer patients. These results demonstrate that the PSMA 624–632 peptide could be an appropriate molecule for use in specific immunotherapy of HLA‐A24+ patients with prostate cancer.