title: Six-transmembrane epithelial antigen of the prostate and enhancer of zeste homolog 2 as immunotherapeutic targets for lung cancer.
abstract: BACKGROUND
  T-cell based immunotherapy for lung cancer (LC) could be a promising and novel therapeutic approach. Six-transmembrane epithelial antigen of the prostate (STEAP) and the polycomb group protein enhancer of zeste homolog 2 (EZH2) are highly expressed in LC and since the expression of molecules in normal tissue is significantly lower as compared to tumor cells, these proteins are considered as potential tumor-associated antigens (TAAs) for developing T-cell based immunotherapy.
  
  
  METHODS
  We assessed the capacity of predicted CD4 T-cell epitopes from STEAP and EZH2 to induce anti-tumor immune responses to LC cell lines.
  
  
  RESULTS
  Out of several predicted epitopes, two synthetic peptides, STEAP281-296 and EZH295-109, were effective in inducing CD4 T-cell responses that were restricted by HLA-DR1, DR15, or DR53 molecules, indicating that the peptides function as promiscuous T-cell epitopes. Moreover, STEAP281-296 and EZH295-109-reactive T-cells could directly recognize STEAP or EZH2 expressing LC cells in an HLA-DR restricted manner. In addition, some STEAP-reactive T-cells responded to STEAP+ tumor cell lysates presented by autologous dendric cells. Most significantly, both of these peptides were capable of stimulating in vitro T-cell responses in patients with LC.
  
  
  CONCLUSIONS
  Peptides STEAP281-296 and EZH295-109 function as strong CD4 T-cell epitopes that can elicit effective anti-tumor T-cell responses against STEAP or EZH2 expressing LC. These observations may facilitate the translation of T-cell based immunotherapy into the clinic for the treatment of LC.
authors: Department of Surgery, Asahikawa Medical University, Asahikawa, Japan. shayashi@asahikawa-med.ac.jp
authors: Satoshi
authors: S
authors: Hayashi
authors: Takumi
authors: T
authors: Kumai
authors: Yoshiya
authors: Y
authors: Matsuda
authors: Naoko
authors: N
authors: Aoki
authors: Keisuke
authors: K
authors: Sato
authors: Shoji
authors: S
authors: Kimura
authors: Masahiro
authors: M
authors: Kitada
authors: Masatoshi
authors: M
authors: Tateno
authors: Esteban
authors: E
authors: Celis
authors: Hiroya
authors: H
authors: Kobayashi
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D000939:Epitopes / Q000276:immunology; D005260:Female; D053804:Granzymes / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000097:blood / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D010088:Oxidoreductases / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D063151:Polycomb Repressive Complex 2; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D000939:Epitopes; D006684:HLA-DR Antigens; D010455:Peptides; D014157:Transcription Factors; D010088:Oxidoreductases; C432763:STEAP1 protein, human; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D053804:Granzymes