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Tumor-targeted interferon-alpha delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis

Academic Article
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Overview

authors

  • 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, Luca
  • Galli, R.
  • Naldini, L.

publication date

  • October 2008

journal

  • Cancer Cell  Journal

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-alpha to tumors. By transplanting hematopoietic progenitors transduced with a Tie2 promoter/enhancer-driven Ifna1 gene, we turned TEMs into IFN-alpha 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-alpha 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-alpha delivery and should allow the development of IFN treatments that more effectively treat cancer.

subject areas

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Genetic Therapy
  • Glioma
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells
  • Humans
  • Immunity, Innate
  • Interferon-alpha
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Monocytes
  • Neoplasm Metastasis
  • Neovascularization, Pathologic
  • Promoter Regions, Genetic
  • Receptor, TIE-2
  • Recombinant Fusion Proteins
  • Time Factors
  • Transduction, Genetic
  • Wound Healing
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Identity

International Standard Serial Number (ISSN)

  • 1878-3686 (Electronic) 1535-6108 (Linking)

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2008.09.004

PubMed ID

  • 18835032
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Additional Document Info

start page

  • 299

end page

  • 311

volume

  • 14

issue

  • 4

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