title: STEAP, a prostate tumor antigen, is a target of human CD8+ T cells.
abstract: STEAP is a recently identified protein shown to be particularly overexpressed in prostate cancer and also present in numerous human cancer cell lines from prostate, pancreas, colon, breast, testicular, cervical, bladder and ovarian carcinoma, acute lymphocytic leukemia and Ewing sarcoma. This expression profile renders STEAP an appealing candidate for broad cancer immunotherapy. In order to investigate if STEAP is a tumor antigen that can be targeted by specific CD8(+) T cells, we identified two high affinity HLA-A*0201 restricted peptides (STEAP(86-94) and STEAP(262-270)). These peptides were immunogenic in vivo in HLA-A*0201 transgenic HHD mice. Peptide specific murine CD8 T cells recognized COS-7 cells co-transfected with HHD (HLA-A*0201) and STEAP cDNA constructs and also HLA-A*0201(+) STEAP(+) human tumor cells. Furthermore, STEAP(86-94) and STEAP(262-270) stimulated specific CD8(+) T cells from HLA-A*0201(+) healthy donors, and these peptide specific CD8(+) T cells recognized STEAP positive human tumor cells in an HLA-A*0201-restricted manner. Importantly, STEAP(86-94)-specific T cells were detected and reactive in the peripheral blood mononuclear cells in NSCLC and prostate cancer patients ex vivo. These results show that STEAP can be a target of anti-tumor CD8(+) T cells and that STEAP peptides can be used for a broad-spectrum-tumor immunotherapy.
authors.affiliation: INSERM 487, Institut Gustave Roussy, 94805, Villejuif, France. pedro.alves@hospvd.ch
authors.forename: Pedro M S
authors.initials: PM
authors.lastname: Alves
authors.forename: Olivier
authors.initials: O
authors.lastname: Faure
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Graff-Dubois
authors.forename: Sebastien
authors.initials: S
authors.lastname: Cornet
authors.forename: Irena
authors.initials: I
authors.lastname: Bolonakis
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Gross
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miconnet
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.forename: Karim
authors.initials: K
authors.lastname: Fizazi
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Kostas
authors.initials: K
authors.lastname: Kosmatopoulos
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology; D045744:Cell Line, Tumor; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010088:Oxidoreductases; D010446:Peptide Fragments / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; C514986:STEAP protein (262-270), human; C514985:STEAP protein (86-94), human; D010088:Oxidoreductases; C432763:STEAP1 protein, human