Induction of human cytotoxic T lymphocytes specific for prostate-specific antigen.
Prostate-specific antigen (PSA), a tissue-specific protein expressed by most adenocarcinomas of the prostate, might be a useful target for T-cell-mediated immunotherapy of prostate cancers. The current study examined whether it is possible to elicit human cytotoxic T lymphocytes (CTL) with specificity for PSA. A synthetic nonamer peptide, corresponding to residues 146-154 of PSA and containing a canonical HLA-A2-binding motif, was shown to stabilize the expression of HLA-A2 on the T2 antigen-processing mutant cell line. Repeated in vitro stimulation of peripheral blood lymphocytes from a normal HLA-A2+ donor induced CTL with specificity for the PSA 146-154 peptide. The peptide-induced CTL expressed the CD4- CD8+ cell surface phenotype and were restricted by HLA-A2. A large portion of patients with prostate cancer express the HLA-A2 phenotype, implying that many prostate cancers might be targeted by HLA-A2-restricted CTL with specificity for the PSA 146-154 epitope.
Xue
B H
BH
Department of Medicine, Loyola University Medical Center, Maywood, Illinois 60153, USA.
Zhang
Y
Y
Sosman
J A
JA
Peace
D J
DJ
D000230:Adenocarcinoma / Q000276:immunology* / Q000628:therapy; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007167:Immunotherapy; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D017430:Prostate-Specific Antigen / Q000737:chemistry / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000939:Epitopes; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D010455:Peptides; C512543:prostate-specific antigen (146-154); D017430:Prostate-Specific Antigen