Author/Authors :
De Palma، نويسنده , , Michele and Mazzieri، نويسنده , , Roberta and Politi، نويسنده , , Letterio S. and Pucci، نويسنده , , Ferdinando and Zonari، نويسنده , , Erika and Sitia، نويسنده , , Giovanni and Mazzoleni، نويسنده , , Stefania and Moi، نويسنده , , Davide and Venneri، نويسنده , , Mary Anna and Indraccolo، نويسنده , , Stefano and Falini، نويسنده , , Andrea and Guidotti، نويسنده , , Luca G. and Galli، نويسنده , , Rossella and Naldini، نويسنده , , Luigi، نويسنده ,
Abstract :
Summary
e 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.
