Identification of a prostate-specific membrane antigen-derived peptide capable of eliciting both cellular and humoral immune responses in HLA-A24+ prostate cancer patients.
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)-gamma 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-gamma 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.
Kobayashi
Kazuhiko
K
Department of Immunology and Department of Urology, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.
Noguchi
Masanori
M
Itoh
Kyogo
K
Harada
Mamoru
M
D000595:Amino Acid Sequence; D000917:Antibody Formation; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology*; D059871:HLA-A24 Antigen; D006801:Humans; D007111:Immunity, Cellular; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D000954:Antigens, Surface; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II