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

被引：254

作者：

De Palma, Michele ^{[1
,2
]}

Mazzieri, Roberta ^{[1
,2
]}

Politi, Letterio S. ^{[5
,6
]}

Pucci, Ferdinando ^{[1
,2
,7
]}

Zonari, Erika ^{[1
,2
]}

Sitia, Giovanni ^{[3
]}

Mazzoleni, Stefania ^{[4
]}

Moi, Davide ^{[1
,2
]}

Venneri, Mary Anna ^{[1
,2
]}

Indraccolo, Stefano ^{[8
]}

Falini, Andrea ^{[5
,6
]}

Guiclotti, Luca G. ^{[3
]}

Galli, Rossella ^{[4
]}

Naldini, Luigi ^{[1
,2
,7
]}

机构：

[1] Angiogenesis & Tumor Targeting Res Unit, I-20132 Milan, Italy

[2] San Raffaele Telethon Inst Gene Therapy HSRTIGET, I-20132 Milan, Italy

[3] Immunopathogenesis Liver Infect Unit, I-20132 Milan, Italy

[4] Ist Sci San Raffaele, Stem Cell Res Inst, I-20132 Milan, Italy

[5] Hosp San Raffaele, Neuroradiol Div, Head & Neck Dept, I-20132 Milan, Italy

[6] Hosp San Raffaele, CERMAC, I-20132 Milan, Italy

[7] Univ Vita Salute San Raffaele, Sch Med, I-20132 Milan, Italy

[8] IRCCS, Ist Oncol Veneto, I-35128 Padua, Italy

来源：

CANCER CELL | 2008年 / 14卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2008.09.004

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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-a 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.

引用

页码：299 / 311

页数：13

共 49 条

[1] Stem and progenitor cell-mediated tumor selective gene therapy [J].

Aboody, K. S. ;

Najbauer, J. ;

Danks, M. K. .

GENE THERAPY, 2008, 15 (10) :739-752

[2] Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: Role of bone marrow-derived myelomonocytic cells [J].

Ahn, G-One ;

Brown, J. Martin .

CANCER CELL, 2008, 13 (03) :193-205

[3] EFFECTS OF MOUSE INTERFERON ON HUMAN-TUMOR XENOGRAFTS IN THE NUDE-MOUSE HOST [J].

BALKWILL, FR ;

PROIETTI, E .

INTERNATIONAL JOURNAL OF CANCER, 1986, 38 (03) :375-380

[4] Interferon-alpha in tumor immunity and immunotherapy [J].

Belardelli, F ;

Ferrantini, M ;

Proietti, E ;

Kirkwood, JM .

CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (02) :119-134

[5] The role of tumor stroma in the interaction between tumor and immune system [J].

Blankenstein, T .

CURRENT OPINION IN IMMUNOLOGY, 2005, 17 (02) :180-186

[6] Stem-cell therapies for blood diseases [J].

Bordignon, Claudio .

NATURE, 2006, 441 (7097) :1100-1102

[7]

Brassard DL, 2002, J LEUKOCYTE BIOL, V71, P565

[8] Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer [J].

Brown, Brian D. ;

Venneri, Mary Anna ;

Zingale, Anna ;

Sergi, Lucia Sergi ;

Naldini, Luigi .

NATURE MEDICINE, 2006, 12 (05) :585-591

[9] Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis [J].

Condeelis, J ;

Pollard, JW .

CELL, 2006, 124 (02) :263-266

[10] Targeted delivery of IFNγ to tumor vessels uncouples antitumor from counterregulatory mechanisms [J].

Curnis, F ;

Gasparri, A ;

Sacchi, A ;

Cattaneo, A ;

Magni, F ;

Corti, A .

CANCER RESEARCH, 2005, 65 (07) :2906-2913

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