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 prosta te 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-O P (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 in duce cytotoxic T cell activity. T cell lines from different HLA-A2 and HLA-A3 donors were established by in vitro stimulation with PSA-OP; t he CTL lines lysed PSA-OP as well as PSA-1- or PSA-3-pulsed C1R-A2 cel ls, and PSA-OP and PSA-9-pulsed C1R-A3 cells, respectively. The CTL li nes derived from the PSA-OP peptide also lysed PSA-positive prostate c ancer cells. PSA-OP-derived T cell lines also lysed recombinant vaccin ia-PSA-infected targets but not targets infected with wild-type vaccin ia, PSA-OP did not bind HLA-A2 and HLA-A3 molecules. The decrease in c ytotoxicity in the presence of protease inhibitors suggests that the P SA-OP is cleaved into shorter peptides, which in turn can interact wit h HLA-class I molecules and, as a consequence, induce CTL-mediated lys is,We have also demonstrated that it is possible to induce CTL respons es in HLA-A2.1/K-b transgenic mice by immunization with PSA-OP with ad juvant. These studies thus provide evidence that oligopeptides such as PSA-OP may be useful candidates for peptide-based cancer vaccines.