title: Administration of DNA Encoding the Interleukin-27 Gene Augments Antitumour Responses through Non-adaptive Immunity.
abstract: DNA-mediated immunization of a tumour antigen is a possible immunotherapy for cancer, and interleukin (IL)-27 has diverse functions in adaptive immunity. In this study, we examined whether IL-27 DNA administration enhanced antitumour effects in mice vaccinated with DNA encoding a putative tumour antigen, β-galactosidase (β-gal). An intramuscular injection of cardiotoxin before DNA administration facilitated the exogenous gene expression. In mice received β-gal and IL-27 DNA, growth of β-gal-positive P815 tumours was retarded and survival of the mice was prolonged. Development of β-gal-positive Colon 26 tumours was suppressed by vaccination of β-gal DNA and further inhibited by additional IL-27 DNA administration or IL-12 family cytokines. Nevertheless, a population of β-gal-specific CD8(+) T cells did not increase, and production of anti-β-gal antibody was not enhanced by IL-27 DNA administration. Spleen cells from mice bearing IL-27-expressing Colon 26 tumours showed greater YAC-1-targeted cytotoxicity although CD3(-)/DX5(+) natural killer (NK) cell numbers remained unchanged. Recombinant IL-27 enhanced YAC-1-targeted cytotoxicity of IL-2-primed splenic NK cells and augmented a phosphorylation of signal transducer and activator of transcription 3 and an expression of perforin. These data collectively indicate that IL-27 DNA administration activates NK cells and augments vaccination effects of DNA encoding a tumour antigen through non-adaptive immune responses.
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan.|Department of Immunology, Hebei Medical University, Shijiazhuang, China.|Cell Therapy Center, The 1st Hospital of Hebei Medical University, Shijiazhuang, China.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.|Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Sato
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Shimozato
authors.affiliation: Department of Thoracic Diseases, Chiba Cancer Center, Chuo-ku, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shingyoji
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tatsumi
authors.affiliation: Department of Surgery, School of Medicine, Toho University, Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Shimada
authors.affiliation: Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden, Yachiyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hiroshima
authors.affiliation: Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Chuo-ku, Chiba, Japan.|Department of Molecular Biology and Oncology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tagawa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use*; D054715:Cardiotoxins / Q000008:administration & dosage; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000235:genetics; D064094:Interleukin-27 / Q000235:genetics*; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009369:Neoplasms / Q000628:therapy*; D054353:Perforin / Q000096:biosynthesis; D010766:Phosphorylation; D050796:STAT3 Transcription Factor / Q000378:metabolism; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology*
chemical_list: D000906:Antibodies; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D054715:Cardiotoxins; D064094:Interleukin-27; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D019444:Vaccines, DNA; D054353:Perforin; D018664:Interleukin-12; D004247:DNA; D001616:beta-Galactosidase