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-Roca; Karin E. deVisser; Antoine Italiano; Christophe LeTourneau; Jean Pierre Delord; Hyam Levitsky; Jean Yves Blay; Dominik Rüttinger

doi:10.1016/j.ccr.2014.05.016

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 journal › Article › peer-review

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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. 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 language	English (US)
Pages (from-to)	846-859
Number of pages	14
Journal	Cancer Cell
Volume	25
Issue number	6
DOIs	https://doi.org/10.1016/j.ccr.2014.05.016
State	Published - Jun 16 2014
Externally published	Yes

ASJC Scopus subject areas

Cancer Research
Cell Biology
Oncology

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Ries, C. H., Cannarile, M. A., Hoves, S., Benz, J., Wartha, K., Runza, V., Rey-Giraud, F., Pradel, L. P., Feuerhake, F., Klaman, I., Jones, T., Jucknischke, U., Scheiblich, S., Kaluza, K., Gorr, I. H., Walz, A., Abiraj, K., Cassier, P. A., Sica, A., ... Rüttinger, D. (2014). Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell, 25(6), 846-859. https://doi.org/10.1016/j.ccr.2014.05.016

Ries, CH, Cannarile, MA, Hoves, S, Benz, J, Wartha, K, Runza, V, Rey-Giraud, F, Pradel, LP, Feuerhake, F, Klaman, I, Jones, T, Jucknischke, U, Scheiblich, S, Kaluza, K, Gorr, IH, Walz, A, Abiraj, K, Cassier, PA, Sica, A, Gomez-Roca, C, deVisser, KE, Italiano, A, LeTourneau, C, Delord, JP, Levitsky, H, Blay, JY & Rüttinger, D 2014, 'Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy', Cancer Cell, vol. 25, no. 6, pp. 846-859. https://doi.org/10.1016/j.ccr.2014.05.016

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

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.",

author = "Ries, {Carola H.} and Cannarile, {Michael A.} and Sabine Hoves and J{\"o}rg Benz and Katharina Wartha and Valeria Runza and Flora Rey-Giraud and Pradel, {Leon P.} and Friedrich Feuerhake and Irina Klaman and Tobin Jones and Ute Jucknischke and Stefan Scheiblich and Klaus Kaluza and Gorr, {Ingo H.} and Antje Walz and Keelara Abiraj and Cassier, {Philippe A.} and Antonio Sica and Carlos Gomez-Roca and deVisser, {Karin E.} and Antoine Italiano and Christophe LeTourneau and Delord, {Jean Pierre} and Hyam Levitsky and Blay, {Jean Yves} and Dominik R{\"u}ttinger",

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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

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.

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

Abstract

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