Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor.
Therapeutic Antibodies Targeting CSF1 Impede Macrophage Recruitment in a Xenograft Model of Tenosynovial Giant Cell Tumor.
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作者：
Cheng H;Clarkson PW;Gao D;Pacheco M;Wang Y;Nielsen TO
肌腱滑膜巨细胞瘤是一种关节肿瘤性疾病，可导致严重的发病率。局部治疗后复发很常见，目前还没有有效的药物治疗方法。最近的研究表明，所有病例都过度表达巨噬细胞集落刺激因子(CSF1)，通常是由于激活的基因易位，导致构成肿瘤主体的巨噬细胞涌入。已经开发了新的抗CSF1药物；然而，还没有适合于评估这种疾病的药物效益的临床前模型。在本文中，我们描述了一种新的肌腱滑膜巨细胞瘤肾被膜下移植模型。利用这一模型，我们证明了抗CSF1单抗可以显著抑制宿主巨噬细胞对肿瘤的侵袭。该模型的结果支持对常规局部治疗无效的肌腱滑膜巨细胞瘤患者进行等效人源化制剂和抗CSF1R小分子药物的临床试验。
Tenosynovial giant cell tumor 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; however there are no preclinical models suitable for evaluation of drug benefits in this disease. In this paper, we describe a novel renal subcapsular 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. The results from this model 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.