title: Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy.
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.
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany. Electronic address: carola.ries@roche.com.
authors.forename: Carola H
authors.initials: CH
authors.lastname: Ries
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cannarile
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoves
authors.affiliation: Roche Innovation Center Basel, Small Molecule Research, Roche Pharmaceutical Research and Early Development, 4070 Basel, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Benz
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wartha
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Valeria
authors.initials: V
authors.lastname: Runza
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Flora
authors.initials: F
authors.lastname: Rey-Giraud
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Leon P
authors.initials: LP
authors.lastname: Pradel
authors.affiliation: Institute for Pathology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Feuerhake
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Klaman
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Tobin
authors.initials: T
authors.lastname: Jones
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Jucknischke
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheiblich
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kaluza
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Gorr
authors.affiliation: Roche Innovation Center Basel, Pharmaceutical Sciences and Oncology Division, Roche Pharmaceutical Research and Early Development, 4070 Basel, Switzerland.
authors.forename: Antje
authors.initials: A
authors.lastname: Walz
authors.affiliation: Roche Innovation Center Basel, Pharmaceutical Sciences and Oncology Division, Roche Pharmaceutical Research and Early Development, 4070 Basel, Switzerland.
authors.forename: Keelara
authors.initials: K
authors.lastname: Abiraj
authors.affiliation: Department of Medicine, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Cassier
authors.affiliation: Humanitas Clinical and Research Center, 20089 Milan, Italy; Department of Pharmaceutical Sciences, University of Piemonte, 28100 Novara, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sica
authors.affiliation: Department of Medicine, Institut Claudius Regaud, 31000 Toulouse, France.
authors.forename: Carlos
authors.initials: C
authors.lastname: Gomez-Roca
authors.affiliation: Division of Immunology, Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands.
authors.forename: Karin E
authors.initials: KE
authors.lastname: de Visser
authors.affiliation: Department of Medical Oncology, Institut Bergonié, 33076 Bordeaux, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Italiano
authors.affiliation: Department of Medical Oncology, Institut Curie, 75248 Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Le Tourneau
authors.affiliation: Department of Medicine, Institut Claudius Regaud, 31000 Toulouse, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Delord
authors.affiliation: Roche Innovation Center Zurich, Oncology Division, Roche Pharmaceutical Research and Early Development, 8952 Zurich, Switzerland.
authors.forename: Hyam
authors.initials: H
authors.lastname: Levitsky
authors.affiliation: Department of Medicine, Centre Léon Bérard, 69008 Lyon, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.affiliation: Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Rüttinger
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D017321:Clinical Trials, Phase I as Topic; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000602304:emactuzumab; D016186:Receptor, Macrophage Colony-Stimulating Factor