title: A tumor lysate is an effective vaccine antigen for the stimulation of CD4(+) T-cell function and subsequent induction of antitumor immunity mediated by CD8(+) T cells.
abstract: To develop a potent cancer vaccine, it is important to study how to prepare highly immunogenic antigens and to identify the most appropriate adjuvants for the antigens. Here we show that a tumor lysate works as an effective antigen to prime CD4(+) T-cell help when baculovirus is employed as an adjuvant. When immunized intradermally with the combination (BLP) of baculovirus, a CT26 tumor lysate, and a cytotoxic T-cell epitope peptide before a tumor challenge, 60% of mice rejected tumors. In contrast, all mice vaccinated with baculovirus plus a tumor lysate (BL) developed tumors. In addition, flow cytometry showed that tumor-specific, interferon γ-producing CD8(+) cytotoxic T lymphocytes (CTLs) were robustly activated by intradermal immunization with BLP. When BLP was administered therapeutically to tumor-bearing mice, antitumor efficacy was better compared to BL. The established tumor was completely eradicated in 50-60% of BLP-treated mice, and induction of tumor-specific CTLs was observed, suggesting that the antitumor efficacy of BLP is mediated by CD8(+) T cells. Numerous CD4(+) T cells infiltrated the tumors of BLP-treated mice, whereas the antitumor effect of BLP almost disappeared after removal of the tumor lysate from BLP or after depletion of BLP-immunized mice of CD4(+) T cells. Thus, the combination of a peptide, lysate, and baculovirus provides stronger antitumor immunity than does a peptide plus baculovirus or a lysate plus baculovirus; effectiveness of BLP is determined by functioning of CD4(+) T cells stimulated with a tumor lysate.
authors.affiliation: a Research and Development Department ; Japan BCG Laboratory ; Kiyose , Tokyo , Japan.|b Department of Life and Environmental Sciences ; Chiba Institute of Technology ; Narashino , Chiba , Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kawahara
authors.affiliation: b Department of Life and Environmental Sciences ; Chiba Institute of Technology ; Narashino , Chiba , Japan.|c High Technology Research Center ; Chiba Institute of Technology ; Narashino , Chiba , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000818:Animals; D016367:Baculoviridae / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D002457:Cell Extracts / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007271:Injections, Intradermal; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*
chemical_list: D019496:Cancer Vaccines; D002457:Cell Extracts; D018984:Epitopes, T-Lymphocyte
keywords: adjuvant; antitumor immunity; baculovirus; immunotherapy; vaccine