Zhang Xuyao, Fan Jiajun, Ju Dianwen
Department of Microbiological and Biochemical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, China.
Antib Ther. 2018 Aug 28;1(2):37-42. doi: 10.1093/abt/tby006. eCollection 2018 Sep.
During the last decade, inhibitors targeting immune checkpoint programmed death ligand 1/PD-1 and cytotoxic T-lymphocyte-associated protein 4 have been one of the most significant advances for cancer therapy in clinic. However, most of these therapies focused on stimulating the adaptive immune system-mediated elimination of tumor. Recent studies indicated that CD47/Signal-regulatory protein alpha (SIRP), an innate anti-phagocytic axis between cancer cells and macrophages, could be a promising therapeutic target. Here, we review the current knowledge about developing CD47/SIRP checkpoint inhibitors, avoiding potential side effect and designing optimal combination therapies, and highlight the key points for future clinical applications of CD47/SIRP axis-targeted tumor immunotherapy.
在过去十年中,靶向免疫检查点程序性死亡配体1/程序性死亡受体1(PD-L1/PD-1)和细胞毒性T淋巴细胞相关蛋白4的抑制剂一直是临床癌症治疗领域最重要的进展之一。然而,这些疗法大多集中于刺激适应性免疫系统介导的肿瘤清除。最近的研究表明,癌细胞与巨噬细胞之间的一种天然抗吞噬轴——CD47/信号调节蛋白α(SIRPα),可能是一个有前景的治疗靶点。在此,我们综述了关于开发CD47/SIRPα检查点抑制剂、避免潜在副作用以及设计最佳联合疗法的现有知识,并强调了CD47/SIRPα轴靶向肿瘤免疫疗法未来临床应用的关键点。