title: Vaccination with liposome-coupled glypican-3-derived epitope peptide stimulates cytotoxic T lymphocytes and inhibits GPC3-expressing tumor growth in mice.
abstract: Because therapeutic manipulation of immunity can induce tumor regression, anti-cancer immunotherapy is considered a promising treatment modality. We previously reported that glypican-3 (GPC3), an oncofetal antigen overexpressed in hepatocellular carcinoma (HCC), is a useful target for cytotoxic T lymphocyte (CTL)-mediated cancer immunotherapy, and we have performed clinical trials using the GPC3-derived peptide vaccine. Although vaccine-induced GPC3-peptide-specific CTLs were often tumor reactive in vitro and were correlated with overall survival, no complete response was observed. In the current study, we synthesized liposome-coupled GPC3-derived CTL epitope peptide (pGPC3-lipsome) and investigated its antitumor potential. Vaccination with pGPC3-liposome induced peptide-specific CTLs at a lower dose than conventional vaccine emulsified in incomplete Freund's adjuvant. Coupling of pGPC3 to liposomes was essential for effective priming of GPC3-specific CTLs. In addition, immunization with pGPC3-liposome inhibited GPC3-expressing tumor growth. Thus, vaccination with tumor-associated antigen-derived epitope peptides coupled to the surfaces of liposomes may be a novel therapeutic strategy for cancer.
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Iwama
authors.affiliation: Department of Microbiology, Saitama Medical University, Iruma-gun, Saitama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan; Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sawada
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan; Department of Gastroenterological Surgery, Graduate School of Medicine, Yokohama City University, Yokohama, Kanagawa, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tsuchiya
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Sugai
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Fujinami
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Shimomura
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan. Electronic address: yuemrua@east.ncc.go.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Uemura
authors.affiliation: Division of Cancer Immunotherapy, Exploratory Oncology Research & Clinical Trial Center National Cancer Center, Kashiwa, Chiba, Japan; Research Institute for Biomedical Sciences, Tokyo University of Science, Japan. Electronic address: tnakatsu@east.ncc.go.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D053673:Glypicans / Q000276:immunology*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination / Q000379:methods
chemical_list: D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; C000602440:GPC3 protein, mouse; D053673:Glypicans; D008081:Liposomes; D010455:Peptides
keywords: Cancer; Glypican-3; Hepatocellular carcinoma; Immunotherapy; Liposome; Peptide vaccine