Adenovirally delivered IFN-β exerts antitumor effects through transient T-lymphocyte depletion and Ag-specific T-cell proliferation

Sang Seok Oh, Chaerin Moon, Dong Hyeok Kim, Hyunkeun Song, Saegwang Park, Yangxin Fu, Kwang Dong Kim

Research output: Contribution to journalArticle

7 Scopus citations

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. Ag104L d 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.

Original languageEnglish (US)
Pages (from-to)1153-1157
Number of pages5
JournalInternational journal of molecular medicine
Volume29
Issue number6
DOIs
StatePublished - Jun 1 2012

Keywords

  • Adenovirus encoding IFN-β
  • Antigen-specific CD8 T cell
  • Transient T lymphocyte depletion
  • Tumor therapy

ASJC Scopus subject areas

  • Genetics

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