title: Analysis of MAGE-3 derived synthetic peptide as a human lung cancer antigen recognized by cytotoxic T lymphocytes.
abstract: BACKGROUND
  The human MAGE-3 gene was originally discovered in melanoma cells that encode tumor antigens, and has been reported to be expressed in various types of tumors, including lung cancer, but not in normal tissues other than testis or placenta. Our aim in this study was to clarify whether HLA-A2 restricted MAGE-3 peptide (FLWGPRALV) could be a lung cancer antigen recognized by cytotoxic T lymphocytes (CTL).
  
  
  METHODS
  MAGE-3-derived peptide-specific CTL were induced from the peripheral blood mononuclear cells (PBMC) of HLA-A0201-positive healthy donors and the regional lymph node lymphocytes (RLNL) of HLA-A2-positive patients with lung cancer by multiple stimulations with peptide-pulsed HLA-A0201-positive antigen-presenting cells.
  
  
  RESULTS
  Lymphocytes stimulated with MAGE-3 peptide exhibited specific lysis of Epstein-Barr virus-transformed B cells (EBV-B) pulsed with MAGE-3 peptide, but not with control peptide derived from influenza matrix protein, erbB-2, or wild type p53. Specific activity for MAGE-3-presenting targets was found after the second stimulation, and increased depending on the number of stimulations. The peptide-specific activity was inhibited by the addition of monoclonal antibodies against MHC class I and HLA-A2. Such CTL also recognized tumor cell lines expressing both HLA-A2 and MAGE-3 in an MHC class I-restricted manner, but did not recognize tumor cell lines that did not express HLA-A2 or MAGE-3.
  
  
  CONCLUSIONS
  These results suggested the MAGE-3 peptide could be a potential target of specific immunotherapy for HLA-A2 patients with lung cancer.
authors.affiliation: Second Department of Surgery, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan. r-eifuku@med.uoeh-u.ac.jp
authors.forename: R
authors.initials: R
authors.lastname: Eifuku
authors.forename: M
authors.initials: M
authors.lastname: Takenoyama
authors.forename: I
authors.initials: I
authors.lastname: Yoshino
authors.forename: S
authors.initials: S
authors.lastname: Imahayashi
authors.forename: T
authors.initials: T
authors.lastname: So
authors.forename: M
authors.initials: M
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Sugaya
authors.forename: K
authors.initials: K
authors.lastname: Yasumoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000032:analysis; D000951:Antigens, Neoplasm; D001402:B-Lymphocytes / Q000276:immunology; D015972:Gene Expression Regulation, Neoplastic; D015789:HLA-A2 Antigen / Q000276:immunology*; D004854:Herpesvirus 4, Human; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology*; D009363:Neoplasm Proteins / Q000032:analysis* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015789:HLA-A2 Antigen; C072013:MAGEA3 protein, human; D009363:Neoplasm Proteins