Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy - PubMed (original) (raw)

. 2014 Jun 16;25(6):846-59.

doi: 10.1016/j.ccr.2014.05.016. Epub 2014 Jun 2.

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

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

Carola H Ries et al. Cancer Cell. 2014.

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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.

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