基因介导的精准免疫疗法在急性髓系白血病治疗中的进展  

Progress of gene-mediated precision immunotherapy in the treatment of acute myeloid leukemia

作　　者：赵鹏博 朱滢 尹莉芳 辛晓斐 ZHAO Pengbo;ZHU Ying;YIN Lifang;XIN Xiaofei(Department of Pharmaceutics,School of Pharmacy,China Pharmaceutical University,Nanjing 210009;Jiangsu Provincial Engineering Research Center for R&D and Evaluation of Intelligent Drugs and Key Functional Excipients,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院药剂系,南京210009 [2]江苏省缓释智能制剂及关键功能性辅料开发与评价工程研究中心,南京210009

出　　处：《中国药科大学学报》2024年第1期53-62,共10页Journal of China Pharmaceutical University

基　　金：国家自然科学基金项目(No.82304410);江苏省自然科学基金项目(No.BK20221045);国家生物药技术创新中心资助项目(No.NCTIB2022HS01015);中国药科大学“双一流”项目。

摘　　要：急性髓系白血病(acute myeloid leukemia,AML)是一种骨髓内造血干细胞的克隆异常,进而导致大量异常分化的髓系细胞在骨髓内聚集而产生的疾病。传统的治疗手段难以治愈AML,嵌合抗原受体T细胞(chimeric antigen receptor Tcell,CAR-T)免疫疗法的成功应用预示着血液肿瘤的治疗进入精准免疫疗法新阶段。然而CAR-T免疫疗法在临床应用中存在诸多问题,例如治疗周期长、价格高昂、产生脱靶效应、发生细胞因子释放综合征等,因此,需要扩展嵌合抗原受体的应用或提出改进措施来提升治疗效果。本文综述了CAR免疫细胞基因工程化改造新策略、原位编辑产生CAR-T的研究进展与应用,同时对体内递送基因药物的新方法进行了简要介绍,旨在为扩展和改进精准免疫疗法在AML中的应用提供新思路和理论依据。Acute myeloid leukemia(AML)is a disease caused by abnormal cloning of hematopoietic stem cells in the bone marrow,which leads to accumulation of a large number of abnormally differentiated myeloid cells.It is difficult to cure by traditional treatment.The successful application of chimeric antigen receptor T cell(CART)immunotherapy indicates that the treatment of hematological tumors has entered a new stage of precision immunotherapy.However,CAR-T immunotherapy has been found to have many problems in clinical applications,including long treatment cycle,expensive prices,off-target effects,cytokine release syndrome,etc.Therefore,it is necessary to expand the application of CAR or adopt improved measures to enhance the therapeutic effect.This article reviews the new strategies for genetic engineering modification of CAR immune cells and the research progress and application of in situ programming to generate CAR-T,and besides,briefly introduces the new methods about the delivery of gene drugs in vivo,aiming to provide new ideas and theoretical basis for expanding and improving the application of precision immunotherapy in AML.

关 键 词：急性髓系白血病 基因编辑 嵌合抗原受体 原位编辑 精准免疫疗法 

分 类 号：R733.7[医药卫生—肿瘤]