Targeting Tumor-Associated Macrophages with Anti-CSF-1R Antibody Reveals a Strategy for Cancer Therapy

被引：1284

作者：

Ries, Carola H. ^{[1
]}

Cannarile, Michael A. ^{[1
]}

Hoves, Sabine ^{[1
]}

Benz, Joerg ^{[2
]}

Wartha, Katharina ^{[1
]}

Runza, Valeria ^{[1
]}

Rey-Giraud, Flora ^{[1
]}

Pradel, Leon P. ^{[1
]}

Feuerhake, Friedrich ^{[3
]}

Klaman, Irina ^{[1
]}

Jones, Tobin ^{[1
]}

Jucknischke, Ute ^{[1
]}

Scheiblich, Stefan ^{[1
]}

Kaluza, Klaus ^{[1
]}

Gorr, Ingo H. ^{[1
]}

Walz, Antje ^{[4
]}

Abiraj, Keelara ^{[4
]}

Cassier, Philippe A. ^{[5
]}

Sica, Antonio ^{[6
,7
]}

Gomez-Roca, Carlos ^{[8
]}

de Visser, Karin E. ^{[9
]}

Italiano, Antoine ^{[10
]}

Le Tourneau, Christophe ^{[11
]}

Delord, Jean-Pierre ^{[8
]}

Levitsky, Hyam ^{[12
]}

Blay, Jean-Yves ^{[5
]}

Ruettinger, Dominik ^{[1
]}

机构：

[1] Roche Pharmaceut Res & Early Dev, Roche Innovat Ctr Penzberg, Div Oncol, D-82377 Penzberg, Germany

[2] Roche Pharmaceut Res & Early Dev, Roche Innovat Ctr Basel, Small Mol Res, CH-4070 Basel, Switzerland

[3] Hannover Med Sch, Inst Pathol, D-30625 Hannover, Germany

[4] Roche Pharmaceut Res & Early Dev, Roche Innovat Ctr Basel, Pharmaceut Sci & Oncol Div, CH-4070 Basel, Switzerland

[5] Ctr Leon Berard, Dept Med, F-69008 Lyon, France

[6] Humanitas Clin & Res Ctr, I-20089 Milan, Italy

[7] Univ Piemonte, Dept Pharmaceut Sci, I-28100 Novara, Italy

[8] Inst Claudius Regaud, Dept Med, F-31000 Toulouse, France

[9] Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands

[10] Inst Bergonie, Dept Med Oncol, F-33076 Bordeaux, France

[11] Inst Curie, Dept Med Oncol, F-75248 Paris, France

[12] Roche Pharmaceut Res & Early Dev, Roche Innovat Ctr Zurich, Div Oncol, CH-8952 Zurich, Switzerland

来源：

CANCER CELL | 2014年 / 25卷 / 06期

关键词：

STIMULATING FACTOR-I; GIANT-CELL TUMOR; STRUCTURAL BASIS; CSF-1; RECEPTOR; BREAST-CANCER; ACTIVATION; EXPRESSION; INHIBITION; IMMUNITY; TRANSLOCATION;

D O I：

10.1016/j.ccr.2014.05.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Macrophage infiltration has been identified as an independent poor prognostic factor in several cancer types. The major survival factor for these macrophages is macrophage colony-stimulating factor 1 (CSF-1). We generated a monoclonal antibody (RG7155) that inhibits CSF-1 receptor (CSF-1R) activation. In vitro RG7155 treatment results in cell death of CSF-1-differentiated macrophages. In animal models, CSF-1R inhibition strongly reduces F4/80(+) tumor-associated macrophages accompanied by an increase of the CD8(+)/CD4(+) T cell ratio. Administration of RG7155 to patients led to striking reductions of CSF-1R(+)CD163(+) macrophages in tumor tissues, which translated into clinical objective responses in diffuse-type giant cell tumor (Dt-GCT) patients.

引用

页码：846 / 859

页数：14

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