Syndax Pharmaceuticals, Inc., Waltham, MA, USA.
Semin Immunol. 2021 Apr;54:101514. doi: 10.1016/j.smim.2021.101514. Epub 2021 Nov 12.
Signaling through colony-stimulating factor 1 receptor (CSF1R) regulates the development, differentiation, and activation of mononuclear phagocytic cells. Inhibition of this pathway provides an opportunity for therapeutic intervention in diseases in which these cells play a pathogenic role, including cancers, inflammation, fibrosis, and others. Multiple monoclonal antibodies and small molecule inhibitors targeting CSF1R or its known ligands CSF1 and IL-34 have been clinically tested and are generally well tolerated with side effects associated with on-target macrophage inhibition or depletion. To date, clinical activity of CSF1R inhibitors has been primarily observed in diffuse-type tenosynovial giant cell tumors, a disease characterized by genetic alterations in CSF1 leading to dysregulated CSF1R signaling. Expanded development into novel indications such as chronic graft vs host disease may provide new opportunities to further explore areas where a role for CSF1R dependent monocytes and macrophages has been established. This review presents key findings from the clinical development of 12 CSF1/CSF1R targeted therapies as monotherapy or in combination with immune checkpoint inhibitors and chemotherapy.
集落刺激因子 1 受体（CSF1R）信号通路调节单核吞噬细胞的发育、分化和激活。抑制该通路为治疗这些细胞发挥致病作用的疾病提供了机会，包括癌症、炎症、纤维化等。针对 CSF1R 或其已知配体 CSF1 和 IL-34 的多种单克隆抗体和小分子抑制剂已在临床上进行了测试，通常具有良好的耐受性，副作用与靶向巨噬细胞抑制或耗竭有关。迄今为止，CSF1R 抑制剂的临床活性主要在弥漫型腱鞘巨细胞瘤中观察到，这种疾病的特征是 CSF1 中的遗传改变导致 CSF1R 信号通路失调。扩展到新的适应症，如慢性移植物抗宿主病，可能为进一步探索 CSF1R 依赖性单核细胞和巨噬细胞发挥作用的领域提供新的机会。本文综述了 12 种 CSF1/CSF1R 靶向治疗药物作为单药或与免疫检查点抑制剂和化疗联合治疗的临床开发中的关键发现。
