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.
Copyright © 2014 Elsevier Inc. All rights reserved.
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