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

Carola H. Ries, Michael A. Cannarile, Sabine Hoves, Jörg Benz, Katharina Wartha, Valeria Runza, Flora Rey-Giraud, Leon P. Pradel, Friedrich Feuerhake, Irina Klaman, Tobin Jones, Ute Jucknischke, Stefan Scheiblich, Klaus Kaluza, Ingo H. Gorr, Antje Walz, Keelara Abiraj, Philippe A. Cassier, Antonio Sica, Carlos Gomez-RocaKarin E. deVisser, Antoine Italiano, Christophe LeTourneau, Jean Pierre Delord, Hyam Levitsky, Jean Yves Blay, Dominik Rüttinger

Research output: Contribution to journalArticlepeer-review

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. Invitro 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+ Tcell 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.

Original languageEnglish
Pages (from-to)846-859
Number of pages14
JournalCancer Cell
Volume25
Issue number6
DOIs
Publication statusPublished - Jun 16 2014

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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