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

doi:10.1016/j.ccr.2008.09.004

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 journal › Article › peer-review

220 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 language	English (US)
Pages (from-to)	299-311
Number of pages	13
Journal	Cancer Cell
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2008.09.004
State	Published - Oct 7 2008
Externally published	Yes

Keywords

CELLCYCLE

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2008.09.004

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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

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title = "Tumor-Targeted Interferon-α Delivery by Tie2-Expressing Monocytes Inhibits Tumor Growth and Metastasis",

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.",

keywords = "CELLCYCLE",

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

note = "Funding Information: We are grateful to M. Bregni and C. Bordignon for helpful discussions; A. Mondino and R. Hess Michelini for help with T cell studies; L. Sergi Sergi for vector production; M. Ponzoni and F. Sanvito for assistance with pathology; and L. Persano, M. Masiero, and E. Hauben for help with some experiments. This research was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Union (FP6 Tumor-Host Genomics), and Telethon to L.N. ",

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doi = "10.1016/j.ccr.2008.09.004",

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T1 - Tumor-Targeted Interferon-α Delivery by Tie2-Expressing Monocytes Inhibits Tumor Growth and Metastasis

AU - De Palma, Michele

AU - Mazzieri, Roberta

AU - Politi, Letterio S.

AU - Pucci, Ferdinando

AU - Zonari, Erika

AU - Sitia, Giovanni

AU - Mazzoleni, Stefania

AU - Moi, Davide

AU - Venneri, Mary Anna

AU - Indraccolo, Stefano

AU - Falini, Andrea

AU - Guidotti, Luca G.

AU - Galli, Rossella

AU - Naldini, Luigi

N1 - Funding Information: We are grateful to M. Bregni and C. Bordignon for helpful discussions; A. Mondino and R. Hess Michelini for help with T cell studies; L. Sergi Sergi for vector production; M. Ponzoni and F. Sanvito for assistance with pathology; and L. Persano, M. Masiero, and E. Hauben for help with some experiments. This research was supported by grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Union (FP6 Tumor-Host Genomics), and Telethon to L.N.

PY - 2008/10/7

Y1 - 2008/10/7

N2 - 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.

AB - 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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JF - Cancer Cell

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ER -

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

Abstract

Keywords

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