Prostate stem cell antigen is a promising candidate for immunotherapy of advanced prostate cancer

Immunotherapy of prostate cancer (CaP) may be a promising novel treatment o ption for the management of advanced Cap, However, the lack of suitable tum or antigens remains a major obstacle for the rational design of vaccines. T o characterize potential CaP antigene, we determined the mRNA expression of the prostate-specific genes CI, C2, C5, PAGE-I, and prostate stem cell ant igen (PSCA) in hormone-refractory CaP, benign prostatic hyperplasia, CaP ce ll lines, and CaP specimens. Among these gene products, only expression of PSCA appears to be retained in the majority of advanced CaP samples, as sho wn by reverse transcription-PCR analyses. Peptide fragments of PSCA present ed in the context of major histocompatibility molecules could serve as reco gnition targets for CD8 T cells, provided these Lymphocytes were not clonal ly deleted or peripherally tolerized. Our goal was to determine whether the human T-cell repertoire could recognize PSCA-derived peptide epitopes in t he context of a common class I allele, HLA-A0201. Of nine peptides that, ac cording to HLA-A0201 binding motifs, were candidate ligands of A0201 class I molecules, three peptides were able to stabilize HLA-A0201 molecules on t he cell surface. One of the latter peptides, encompassing amino acid residu es 14-22, was capable of generating a PSCA-specific T-cell response in a hu man lymphocyte culture from a patient with metastatic CaP, PSCA-specific CT Ls recognized peptide-pulsed targets as well as three prostate carcinoma li nes in cytotoxicity assays, indicating that this peptide could be endogenou sly processed. In conclusion, our findings establish PSCA as a potential ta rget for antigen-specific, T cell-based immunotherapy of prostate carcinoma .