title: Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors.
abstract: OBJECTIVE
  CD26 is a 110-kDa cell surface antigen with a role in tumor development. In this report, we show that CD26 is highly expressed on the cell surface of malignant mesothelioma and that a newly developed humanized anti-CD26 monoclonal antibody (mAb) has an inhibitory effect on malignant mesothelioma cells in both in vitro and in vivo experiments.
  
  
  METHODS
  Using immunohistochemistry, 12 patients' surgical specimens consisting of seven malignant mesothelioma, three reactive mesothelial cells, and two adenomatoid tumors were evaluated for expression of CD26. The effects of CD26 on malignant mesothelioma cells were assessed in the presence of transfection of CD26-expressing plasmid, humanized anti-CD26 mAb, or small interfering RNA against CD26. The in vivo growth inhibitory effect of humanized anti-CD26 mAb was assessed in human malignant mesothelioma cell mouse xenograft models.
  
  
  RESULTS
  In surgical specimens, CD26 is highly expressed in malignant mesothelioma but not in benign mesothelial tissues. Depletion of CD26 by small interfering RNA results in the loss of adhesive property, suggesting that CD26 is a binding protein to the extracellular matrix. Moreover, our in vitro data indicate that humanized anti-CD26 mAb induces cell lysis of malignant mesothelioma cells via antibody-dependent cell-mediated cytotoxicity in addition to its direct anti-tumor effect via p27(kip1) accumulation. In vivo experiments with mouse xenograft models involving human malignant mesothelioma cells show that humanized anti-CD26 mAb treatment drastically inhibits tumor growth in tumor-bearing mice, resulting in enhanced survival.
  
  
  CONCLUSIONS
  Our data strongly suggest that humanized anti-CD26 mAb treatment may have potential clinical use as a novel cancer therapeutic agent in CD26-positive malignant mesothelioma.
authors.affiliation: Division of Clinical Immunology, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Inamoto
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Kei
authors.initials: K
authors.lastname: Ohnuma
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Kina
authors.forename: Nozomu
authors.initials: N
authors.lastname: Takahashi
authors.forename: Tadanori
authors.initials: T
authors.lastname: Yamochi
authors.forename: Sakiko
authors.initials: S
authors.lastname: Inamoto
authors.forename: Yoji
authors.initials: Y
authors.lastname: Katsuoka
authors.forename: Osamu
authors.initials: O
authors.lastname: Hosono
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nam H
authors.initials: NH
authors.lastname: Dang
authors.forename: Chikao
authors.initials: C
authors.lastname: Morimoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007150:Immunohistochemistry; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008654:Mesothelioma / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018819:Dipeptidyl Peptidase 4