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. Prostate 30:73–78, 1997. © 1997 Wiley‐Liss, Inc.