title: Mouse homologue of a novel human oncofetal antigen, glypican-3, evokes T-cell-mediated tumor rejection without autoimmune reactions in mice.
abstract: OBJECTIVE
  We recently identified glypican-3 (GPC3) overexpressed specifically in human hepatocellular carcinoma, as based on cDNA microarray analysis of 23,040 genes, and we reported that GPC3 is a novel tumor marker for human hepatocellular carcinoma and melanoma. GPC3, expressed in almost all hepatocellular carcinomas and melanomas, but not in normal tissues except for placenta or fetal liver, is a candidate of ideal tumor antigen for immunotherapy. In this study, we attempted to identify a mouse GPC3 epitope for CTLs in BALB/c mice, and for this, we set up a preclinical study to investigate the usefulness of GPC3 as a target for cancer immunotherapy in vivo.
  
  
  RESULTS
  We identified a mouse GPC3-derived and Kd- restricted CTL epitope peptide in BALB/c mice. Inoculation of this GPC3 peptide-specific CTL into s.c. Colon26 cancer cells transfected with mouse GPC3 gene (C26/GPC3) led to rejection of the tumor in vivo, and i.v. inoculation of these CTLs into sublethally irradiated mice markedly inhibited growth of an established s.c. tumor. Inoculation of bone marrow-derived dendritic cells pulsed with this peptide prevented the growth of s.c. and splenic C26/GPC3 accompanied with massive infiltration of CD8+ T cells into tumors. Evidence of autoimmune reactions was never observed in surviving mice that had rejected tumor cell challenges.
  
  
  CONCLUSIONS
  We found the novel oncofetal protein GPC3 to be highly immunogenic in mice and elicited effective antitumor immunity with no evidence of autoimmunity. GPC3 is useful not only for diagnosis of hepatocellular carcinoma and melanoma but also for possible immunotherapy or prevention of these tumors.
authors.affiliation: Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Komori
authors.forename: Tatsuko
authors.initials: T
authors.lastname: Kubo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yoshitake
authors.forename: Satoru
authors.initials: S
authors.lastname: Senju
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Furukawa
authors.forename: Michio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D015551:Autoimmunity; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D003713:Dendritic Cells / Q000276:immunology; D053673:Glypicans; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology* / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010446:Peptide Fragments; C031192:oncofetal antigens