Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
Roche Innovation Center Penzberg, Oncology Division, Roche Pharmaceutical Research and Early Development, 82377 Penzberg, Germany.
Cancer Cell. 2014 Jun 16;25(6):846-59. doi: 10.1016/j.ccr.2014.05.016. Epub 2014 Jun 2.
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.
巨噬细胞浸润已被确定为几种癌症类型的独立预后不良因素。这些巨噬细胞的主要生存因素是巨噬细胞集落刺激因子 1（CSF-1）。我们生成了一种单克隆抗体（RG7155），可抑制 CSF-1 受体（CSF-1R）的激活。体外 RG7155 处理导致 CSF-1 分化的巨噬细胞死亡。在动物模型中，CSF-1R 抑制强烈减少 F4/80（+）肿瘤相关巨噬细胞，同时增加 CD8（+）/CD4（+）T 细胞比值。将 RG7155 施用于患者导致肿瘤组织中 CSF-1R（+）CD163（+）巨噬细胞明显减少，这在弥漫性巨细胞瘤（Dt-GCT）患者中转化为临床客观反应。
