title: Identification of prostate-specific G-protein coupled receptor as a tumor antigen recognized by CD8(+) T cells for cancer immunotherapy.
abstract: BACKGROUND
  Prostate cancer is the most common cancer among elderly men in the US, and immunotherapy has been shown to be a promising strategy to treat patients with metastatic castration-resistant prostate cancer. Efforts to identify novel prostate specific tumor antigens will facilitate the development of effective cancer vaccines against prostate cancer. Prostate-specific G-protein coupled receptor (PSGR) is a novel antigen that has been shown to be specifically over-expressed in human prostate cancer tissues. In this study, we describe the identification of PSGR-derived peptide epitopes recognized by CD8(+) T cells in an HLA-A2 dependent manner.
  
  
  RESULTS
  Twenty-one PSGR-derived peptides were predicted by an immuno-informatics approach based on the HLA-A2 binding motif. These peptides were examined for their ability to induce peptide-specific T cell responses in peripheral blood mononuclear cells (PBMCs) obtained from either HLA-A2(+) healthy donors or HLA-A2(+) prostate cancer patients. The recognition of HLA-A2 positive and PSGR expressing LNCaP cells was also tested. Among the 21 PSGR-derived peptides, three peptides, PSGR3, PSGR4 and PSGR14 frequently induced peptide-specific T cell responses in PBMCs from both healthy donors and prostate cancer patients. Importantly, these peptide-specific T cells recognized and killed LNCaP prostate cancer cells in an HLA class I-restricted manner.
  
  
  CONCLUSIONS
  We have identified three novel HLA-A2-restricted PSGR-derived peptides recognized by CD8(+) T cells, which, in turn, recognize HLA-A2(+) and PSGR(+) tumor cells. The PSGR-derived peptides identified may be used as diagnostic markers as well as immune targets for development of anticancer vaccines.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.forename: Mingjun
authors.initials: M
authors.lastname: Wang
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Weng
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Bingnan
authors.initials: B
authors.lastname: Yin
authors.forename: Jia
authors.initials: J
authors.lastname: Zou
authors.forename: Qingtian
authors.initials: Q
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.forename: Weiyi
authors.initials: W
authors.lastname: Peng
authors.forename: Xavier
authors.initials: X
authors.lastname: Legras
authors.forename: Christopher
authors.initials: C
authors.lastname: Loo
authors.forename: Rong-Fu
authors.initials: RF
authors.lastname: Wang
authors.forename: Helen Y
authors.initials: HY
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019496:Cancer Vaccines / Q000138:chemical synthesis / Q000276:immunology*; D045744:Cell Line, Tumor; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D018035:Receptors, Odorant / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006680:HLA Antigens; D009363:Neoplasm Proteins; C417566:OR51E2 protein, human; D010446:Peptide Fragments; D018035:Receptors, Odorant; D007371:Interferon-gamma