[PDF][PDF] Tumor-targeted interferon-α delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis

M De Palma, R Mazzieri, LS Politi, F Pucci, E Zonari… - Cancer cell, 2008 - cell.com
M De Palma, R Mazzieri, LS Politi, F Pucci, E Zonari, G Sitia, S Mazzoleni, D Moi…
Cancer cell, 2008cell.com
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 …
Summary
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.
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