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

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

  • Cancer Cell. 2014 Jun 16;25(6):846-59. doi: 10.1016/j.ccr.2014.05.016.
Carola H Ries 1,  Michael A Cannarile 2,  Sabine Hoves 2,  Jörg Benz 3,  Katharina Wartha 2,  Valeria Runza 2,  Flora Rey-Giraud 2,  Leon P Pradel 2,  Friedrich Feuerhake 4,  Irina Klaman 2,  Tobin Jones 2,  Ute Jucknischke 2,  Stefan Scheiblich 2,  Klaus Kaluza 2,  Ingo H Gorr 2,  Antje Walz 5,  Keelara Abiraj 5,  Philippe A Cassier 6,  Antonio Sica 7,  Carlos Gomez-Roca 8,  Karin E de Visser 9,  Antoine Italiano 10,  Christophe Le Tourneau 11,  Jean-Pierre Delord 8,  Hyam Levitsky 12,  Jean-Yves Blay 6,  Dominik Rüttinger 2
Affiliations

Affiliations

  • 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.
PMID: 24898549 DOI: 10.1016/j.ccr.2014.05.016
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.

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