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. Epub 2014 Jun 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Monoclonal / pharmacokinetics
  • Antibodies, Monoclonal / pharmacology*
  • Antibodies, Monoclonal, Humanized
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Clinical Trials, Phase I as Topic
  • Cohort Studies
  • Colonic Neoplasms / immunology
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / therapy*
  • Female
  • Humans
  • Macaca fascicularis
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Male
  • Mice, Inbred C57BL
  • Models, Molecular
  • Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Receptor, Macrophage Colony-Stimulating Factor / immunology*
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • emactuzumab
  • Receptor, Macrophage Colony-Stimulating Factor

Associated data

  • ClinicalTrials.gov/NCT01494688