title: Adenovirally delivered IFN-β exerts antitumor effects through transient             T-lymphocyte depletion and Ag-specific T-cell proliferation.
abstract: Type I interferons (IFNs), including IFN-β, are known to enhance antigen (Ag) presentation and to promote the expansion, survival and effector function of CD8+ cytotoxic lymphocytes (CTL) during viral infections. Furthermore, IFN-β is a potent candidate for antitumor drugs; however, recombinant IFN-β is too unstable for use in tumor therapy in vivo. In this study, we therefore examined the efficacy and mechanism of exogenous IFN-β as a biomolecule for tumor therapy, using adenovirus encoding IFN-β (Ad-IFNβ) as a therapeutic agent in a mouse model. Ag104Ld and 4T1 tumor cells exposed to Ad-IFNβ showed growth retardation and cell death in vitro, and tumor growth as well as tumor metastasis was inhibited in vivo. The Ad-IFNβ-mediated antitumor effect was dependent on CD8+ T cells in vivo, rather than on a direct cytotoxic effect of Ad-IFNβ. Transient T lymphocyte depletion was observed in tumor tissue after intratumoral injection with Ad-IFNβ. Despite the T lymphocyte depletion, the proliferation of Ag-specific CD8+ T cells was increased in Ad-IFNβ-treated mice compared to control virus-treated mice. These results suggest that IFN-β might contribute to the inhibition of tumor growth by depleting Ag-nonspecific T lymphocytes and enhancing proliferation of Ag-specific CD8+ T cells.
authors.affiliation: Division of Applied Life Science (BK21), PMBBRC, Gyeongsang National                     University, Jinju, Republic of Korea.
authors.forename: Sang-Seok
authors.initials: SS
authors.lastname: Oh
authors.forename: Chaerin
authors.initials: C
authors.lastname: Moon
authors.forename: Dong-Hyeok
authors.initials: DH
authors.lastname: Kim
authors.forename: Hyunkeun
authors.initials: H
authors.lastname: Song
authors.forename: Saegwang
authors.initials: S
authors.lastname: Park
authors.forename: Yangxin
authors.initials: Y
authors.lastname: Fu
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000235:genetics*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes / Q000187:drug effects / Q000276:immunology*; D015316:Genetic Therapy; D006801:Humans; D016899:Interferon-beta / Q000235:genetics* / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D012074:Remission Induction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D047368:Tumor Burden / Q000276:immunology; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D000939:Epitopes; D016899:Interferon-beta