免疫检查点LAG-3及其靶向药物研究现状和临床应用进展  

Current research status and clinical application progress of the immune checkpoint LAG-3 and its targeting drugs

作　　者：周慧男 钦可为 周丽君 ZHOU Huinan;QIN Kewei;ZHOU Lijun(Central Laboratory,the Sixth Medical Centre,Chinese PLA General Hospital,Beijing 100048,China;The Second School of Clinical Medicine,Southern Medical University,Guangzhou 510515,China)

机构地区：[1]中国人民解放军总医院第六医学中心耳鼻喉头颈外科医学部研究所,北京100048 [2]南方医科大学第二临床医学院,广州510280

出　　处：《实用医学杂志》2024年第11期1607-1612,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:32170933,82202382);北京市自然科学基金资助项目(编号:7242135)。

摘　　要：淋巴细胞激活基因3(lymphocyte-activation gene 3,LAG-3)是一种抑制性免疫检查点受体,能负向调控T细胞的功能,避免免疫系统过度激活损伤机体。当肿瘤和慢性感染存在时,持续的抗原刺激诱导效应T细胞的LAG-3表达上调进而导致T细胞功能耗竭和肿瘤免疫逃逸。靶向LAG-3药物通过特异性阻断LAG-3的信号通路,能重新激活T细胞的抗肿瘤功能,在多种实体瘤、血液系统肿瘤及自身免疫性疾病中均有很好的疗效。本文总结了当前关于LAG-3的结构,配体和调控功能机制的研究进展,对当前的靶向LAG-3药物临床试验现状进行综述,讨论了LAG-3靶向药物的临床应用策略和发展方向,以期为进一步深入研究LAG-3提供参考。Lymphocyte-activation gene 3(LAG-3)is an inhibitory immune checkpoint receptor that negatively regulates the function of T cells to prevent over-activation of the immune system from damaging human body.In the existence of tumors and chronic infections,persistent antigenic stimulation induces upregulation of LAG-3 expression in effector T cells,leading to T cell exhaustion and tumor immune escape.Targeting LAG-3 drugs can reactivate the anti-tumor function of T cells by specifically blocking the signaling pathway of LAG-3,and have shown promising efficacy in a variety of solid tumors,hematologic tumors and autoimmune diseases.In this paper,we summarize the current research progress on the structure,ligand and regulatory function of LAG-3,review the current status of clinical trials of LAG-3-targeted drugs,and further discuss the clinical application strategy and development direction of LAG-3-targeted drugs,with a view to providing reference for further in-depth research on LAG-3.

关 键 词：淋巴细胞活化基因3 免疫检查点 肿瘤 治疗性抗体 

分 类 号：R730.5[医药卫生—肿瘤]