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Therapeutic antibodies targeting CSF1 impede macrophage recruitment in a xenograft model of tenosynovial giant cell tumor

Clarkson, Paul and Cheng, Hongwei and West, Robert and Gao, Doris and Wang, Y.Z. and Nielsen, Torsten and Abraham, Judith (2010) Therapeutic antibodies targeting CSF1 impede macrophage recruitment in a xenograft model of tenosynovial giant cell tumor. Sarcoma, 2010 (Octobe).

Abstract

Tenosynovial giant cell tumor / pigmented villonodular synovitis (PVNS) is a neoplastic disease of joints that can cause severe morbidity. Recurrences are common following local therapy, and no effective medical therapy currently exists. Recent work has demonstrated that all cases overexpress macrophage colony stimulating factor (CSF1), usually as a consequence of an activating gene translocation, resulting in an influx of macrophages that form the bulk of the tumor. New anti-CSF1 drugs have been developed, and PVNS is an ideal index disease for evaluating their therapeutic benefit. However, no preclinical models suitable for evaluation of drug benefits in this disease currently exist. In this report, we describe a novel renal subcapsular primary tumor xenograft model of tenosynovial giant cell tumor. Using this model, we demonstrate that an anti-CSF1 monoclonal antibody significantly inhibits host macrophage infiltration into this tumor. This model and data can be used to support clinical trials of equivalent humanized agents and anti-CSF1R small molecule drugs in cases of tenosynovial giant cell tumor refractory to conventional local therapy.

Item Type: Article
Keywords: macrophage colony-stimulating factor, M-CSF, CSF-1R, pigmented villonodular synovitis, PVNS
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2515

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