TY - JOUR
T1 - Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy
AU - Ries, Carola H.
AU - Cannarile, Michael A.
AU - Hoves, Sabine
AU - Benz, Jörg
AU - Wartha, Katharina
AU - Runza, Valeria
AU - Rey-Giraud, Flora
AU - Pradel, Leon P.
AU - Feuerhake, Friedrich
AU - Klaman, Irina
AU - Jones, Tobin
AU - Jucknischke, Ute
AU - Scheiblich, Stefan
AU - Kaluza, Klaus
AU - Gorr, Ingo H.
AU - Walz, Antje
AU - Abiraj, Keelara
AU - Cassier, Philippe A.
AU - Sica, Antonio
AU - Gomez-Roca, Carlos
AU - deVisser, Karin E.
AU - Italiano, Antoine
AU - LeTourneau, Christophe
AU - Delord, Jean Pierre
AU - Levitsky, Hyam
AU - Blay, Jean Yves
AU - Rüttinger, Dominik
N1 - Funding Information:
We thank Hubert Hertenberger for his support of crystallization efforts, Claudia Kirstenpfad for her work on macrophages, Alexander Fidler and Gudrun Geiselmann for performing hybridoma screening, Maria Grazia Totaro and Theresia Manger-Harasim for their work on the mouse models, Barbara Threm for flow cytometry analyses, Tisee Hau for IHC analysis, Sandra Bunte for T cell isolation, Dominqiue Burger for protein analytics, Expose and the team at the beam line X10SA of the Swiss Light Source in Villigen, Dr. Stefan Ries for valuable strategic advice and review, Dr. Ann-Marie Broeske for scientific support, the Study Management team for managing the phase 1 clinical trial, Dr. Mike Burgess for supporting the clinical development of RG7155, Dr. Sascha Dimitrijevic for helpful discussions, and Dr. John C. Reed for critical review. We thank Dr. Pin Lu (Rx Communications, Mold, UK), who provided support in formatting the manuscript funded by Roche. C.H.R., M.A.C., S.H., J.B., K.W., V.R., F.R.-G., L.P.P., F.F., I.K., T.J., U.J., S.S., K.K., I.H.G., A.W., K.A., H.L., and D.R. are or have been employees of Roche. The clinical trial was funded by F. Hoffmann-La Roche AG. A.S., K.E.d.V., and J.Y.B. received research support from Roche.
PY - 2014/6/16
Y1 - 2014/6/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84902546715&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2014.05.016
DO - 10.1016/j.ccr.2014.05.016
M3 - Article
SN - 1535-6108
VL - 25
SP - 846
EP - 859
JO - Cancer Cell
JF - Cancer Cell
IS - 6
ER -
