Generation of human cytolytic T lymphocyte lines directed against prostate-specific antigen (PSA) employing a PSA oligoepitope peptide.
Prostate-specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity. T cell lines from different HLA-A2 and HLA-A3 donors were established by in vitro stimulation with PSA-OP; the CTL lines lysed PSA-OP as well as PSA-1- or PSA-3-pulsed C1R-A2 cells, and PSA-OP and PSA-9-pulsed C1R-A3 cells, respectively. The CTL lines derived from the PSA-OP peptide also lysed PSA-positive prostate cancer cells. PSA-OP-derived T cell lines also lysed recombinant vaccinia-PSA-infected targets but not targets infected with wild-type vaccinia. PSA-OP did not bind HLA-A2 and HLA-A3 molecules. The decrease in cytotoxicity in the presence of protease inhibitors suggests that the PSA-OP is cleaved into shorter peptides, which in turn can interact with HLA-class I molecules and, as a consequence, induce CTL-mediated lysis. We have also demonstrated that it is possible to induce CTL responses in HLA-A2.1/Kb transgenic mice by immunization with PSA-OP with adjuvant. These studies thus provide evidence that oligopeptides such as PSA-OP may be useful candidates for peptide-based cancer vaccines.
Correale
P
P
Laboratory of Tumor Immunology and Biology, Division of Basic Science, National Cancer Institute, Bethesda, MD 20892, USA.
Walmsley
K
K
Zaremba
S
S
Zhu
M
M
Schlom
J
J
Tsang
K Y
KY
D000595:Amino Acid Sequence; D000818:Animals; D002277:Carcinoma / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000235:genetics / Q000276:immunology*; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology; D011480:Protease Inhibitors / Q000494:pharmacology; D011995:Recombination, Genetic / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000201:enzymology / Q000276:immunology*; D014407:Tumor Cells, Cultured; D014616:Vaccinia virus / Q000235:genetics
D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D016056:Immunodominant Epitopes; D009842:Oligopeptides; D011480:Protease Inhibitors; D017430:Prostate-Specific Antigen