Identification of an H2-Kb or H2-Db restricted and glypican-3-derived             cytotoxic T-lymphocyte epitope peptide.
Glypican-3 (GPC3) is overexpressed in human hepatocellular carcinoma (HCC)             but not expressed in normal tissues except for placenta and fetal liver and therefore             is an ideal target for cancer immunotherapy. In this study, we identified an H2-Kb             or H2-Db restricted and murine GPC3 (mGPC3)-derived cytotoxic T-lymphocyte (CTL)             epitope peptide in C57BL/6 (B6) mice, which can be used in the design of preclinical             studies of various therapies with GPC3-target immunotherapy in vivo. First, 11             types of 9- to 10-mer peptides predicted to bind with H2-Kb or H2-Db were selected             from the mGPC3 amino acid sequence based on the binding score as calculated by             the BIMAS software. We evaluated the peptide-binding affinity and confirmed that             all peptides were able to bind to H2-Kb or H2-Db by in vitro cellular binding             assay. Subsequently, a mixed peptide vaccine and single peptide vaccine were given             to B6 mice to evaluate immunogenic potential of the 11 selected peptides. Using             the splenocytes from peptide-vaccinated mice, interferon (IFN)-γ enzyme-linked             immunospot (ELISPOT) assays showed that mGPC3-1127-136 (AMFKNNYPSL) peptide was             the most efficient for inducing CTLs among the 11 peptides. Next, we demonstrated             that the mGPC3-1 peptide-specific CTL line could recognize mGPC3-expressing cancer             cells, suggesting that mGPC3-1 peptide was an endogenously presented peptide.             In conclusion, we identified mGPC3-1 as an H2-Kb or H2-Db restricted, mGPC3-derived             CTL epitope peptide.
Division of Cancer Immunotherapy, Research Center for Innovative                     Oncology, National Cancer Center Hospital East, Kashiwa, Chiba 277-8577,                     Japan.
Tatsuaki
T
Iwama
Kazutaka
K
Horie
Toshiaki
T
Yoshikawa
Daisuke
D
Nobuoka
Manami
M
Shimomura
Yu
Y
Sawada
Tetsuya
T
Nakatsura
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy; D045744:Cell Line, Tumor; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D005260:Female; D053673:Glypicans / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000276:immunology* / Q000378:metabolism; D064532:Histocompatibility Antigen H-2D; D007167:Immunotherapy; D007371:Interferon-gamma / Q000032:analysis; D008113:Liver Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology; D011485:Protein Binding; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D053673:Glypicans; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D064532:Histocompatibility Antigen H-2D; D010446:Peptide Fragments; D022223:Vaccines, Subunit; D007371:Interferon-gamma