Tumor-Targeted Interferon-α Delivery by Tie2-Expressing Monocytes Inhibits Tumor Growth and Metastasis

Michele De Palma, Roberta Mazzieri, Letterio S. Politi, Ferdinando Pucci, Erika Zonari, Giovanni Sitia, Stefania Mazzoleni, Davide Moi, Mary Anna Venneri, Stefano Indraccolo, Andrea Falini, Luca G. Guidotti, Rossella Galli, Luigi Naldini

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

The use of type I interferons (IFNs) in cancer therapy has been limited by ineffective dosing and significant toxicity. Here, we exploited the tumor-homing ability of proangiogenic Tie2-expressing monocytes (TEMs) to deliver IFN-α to tumors. By transplanting hematopoietic progenitors transduced with a Tie2 promoter/enhancer-driven Ifna1 gene, we turned TEMs into IFN-α cell vehicles that efficiently targeted the IFN response to orthotopic human gliomas and spontaneous mouse mammary carcinomas and obtained significant antitumor responses and near complete abrogation of metastasis. TEM-mediated IFN-α delivery inhibited tumor angiogenesis and activated innate and adaptive immune cells but did not impair myelopoiesis and wound healing detectably. These results illustrate the therapeutic potential of gene- and cell-based IFN-α delivery and should allow the development of IFN treatments that more effectively treat cancer.

Original languageEnglish (US)
Pages (from-to)299-311
Number of pages13
JournalCancer Cell
Volume14
Issue number4
DOIs
StatePublished - Oct 7 2008

Keywords

  • CELLCYCLE

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    De Palma, M., Mazzieri, R., Politi, L. S., Pucci, F., Zonari, E., Sitia, G., Mazzoleni, S., Moi, D., Venneri, M. A., Indraccolo, S., Falini, A., Guidotti, L. G., Galli, R., & Naldini, L. (2008). Tumor-Targeted Interferon-α Delivery by Tie2-Expressing Monocytes Inhibits Tumor Growth and Metastasis. Cancer Cell, 14(4), 299-311. https://doi.org/10.1016/j.ccr.2008.09.004