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Cancer Cell. 2014 Jun 16;25(6):846-59. doi: 10.1016/j.ccr.2014.05.016. Epub 2014 Jun 2.

Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.

Author information

1
Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany. Electronic address: carola.ries@roche.com.
2
Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
3
Roche Innovation Center Basel, Small Molecule Research, Roche Pharmaceutical Research and Early Development, 4070 Basel, Switzerland.
4
Institute for Pathology, Hannover Medical School, 30625 Hannover, Germany.
5
Roche Innovation Center Basel, Pharmaceutical Sciences and Oncology Division, Roche Pharmaceutical Research and Early Development, 4070 Basel, Switzerland.
6
Department of Medicine, Centre Léon Bérard, 69008 Lyon, France.
7
Humanitas Clinical and Research Center, 20089 Milan, Italy; Department of Pharmaceutical Sciences, University of Piemonte, 28100 Novara, Italy.
8
Department of Medicine, Institut Claudius Regaud, 31000 Toulouse, France.
9
Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
10
Department of Medical Oncology, Institut Bergonié, 33076 Bordeaux, France.
11
Department of Medical Oncology, Institut Curie, 75248 Paris, France.
12
Roche Innovation Center Zurich, Oncology Division, Roche Pharmaceutical Research and Early Development, 8952 Zurich, Switzerland.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01494688.

PMID:
24898549
DOI:
10.1016/j.ccr.2014.05.016
[Indexed for MEDLINE]
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