Antitumor activity of recombinant adenoviral vectors expressing murine IFN-α in mice injected with metastatic IFN-resistant tumor cells

Laura Santodonato, Maria Ferrantini, Fabio Palombo, Luigi Aurisicchio, Paola Delmastro, Nicola La Monica, Stefania Di Marco, Gennaro Ciliberto, Mark X. Du, Milton W. Taylor, Filippo Belardelli

Research output: Contribution to journalArticle

Abstract

Recent studies have shown that gene therapy with type I interferon (IFN) in an adenovirus vector is a powerful tool to suppress the growth of human tumors transplanted in immune-deficient mice. However, in these studies the host immune-mediated effects, which may be important in mediating the long-term control of tumor growth by these cytokines, was not studied. In this paper, we evaluate the antitumor efficacy of different adenoviral vectors containing mouse IFN-α genes (i.e., a first-generation replication-defective vector containing IFN-α1 and two different second-generation vectors containing IFN-α2) in immunocompetent DBA/2 mice transplanted with highly metastatic Friend leukemic cells resistant in vitro to type I IFN. We found that injection of all the different adenovirus vectors containing mouse IFN-α genes resulted in a marked antitumor response in mice transplanted either subcutaneously or intravenously with IFN-resistant Friend leukemic cells compared to tumor-bearing animals inoculated with a control vector. Tumor growth inhibition after injection of IFN-adenovirus vectors was associated with a prolonged presence of high IFN levels in the sera of the injected mice. Suppression of metastatic tumor growth was also observed after a single injection of the IFN-adenovirus recombinant vectors, whereas a comparable antitumor response generally required several injections of high doses of IFN. Altogether, these results demonstrate that IFN-adenoviral vectors can efficiently inhibit metastatic tumor growth by host-mediated mechanisms and suggest that adenovirus-mediated IFN-α gene therapy may represent an attractive alternative to the conventional clinical use of this cytokine, which generally requires multiple injections of high IFN doses for a prolonged period of time.

Original languageEnglish
Pages (from-to)63-72
Number of pages10
JournalCancer Gene Therapy
Volume8
Issue number1
Publication statusPublished - 2001

Keywords

  • Adenoviral vectors
  • Gene therapy
  • IFN-α
  • Mice
  • Tumor

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

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    Santodonato, L., Ferrantini, M., Palombo, F., Aurisicchio, L., Delmastro, P., La Monica, N., Di Marco, S., Ciliberto, G., Du, M. X., Taylor, M. W., & Belardelli, F. (2001). Antitumor activity of recombinant adenoviral vectors expressing murine IFN-α in mice injected with metastatic IFN-resistant tumor cells. Cancer Gene Therapy, 8(1), 63-72.