| Literature DB >> 18835032 |
Michele De Palma1, 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.
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.Entities:
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Year: 2008 PMID： 18835032 DOI： 10.1016/j.ccr.2008.09.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743