Induction of human cytotoxic T lymphocytes specific for prostate-specific antigen

Abstract

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.