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作 者:周潇 潘晟 凌孙彬 徐骁[2] 卫强 ZHOU Xiao;PAN Sheng;LING Sunbin;XU Xiao;WEI Qiang(The Fourth School of Clinical Medicine,Zhejiang Chinese Medicine University,Hangzhou First People's Hospital,Hangzhou 310006,China;School of Medicine,Zhejiang University,Hangzhou 310058,China)
机构地区:[1]浙江中医药大学第四临床医学院,杭州市第一人民医院,浙江杭州310006 [2]浙江大学医学院,浙江杭州310058
出 处:《中国肿瘤》2025年第2期152-158,共7页China Cancer
基 金:浙江省重点研发计划项目(2021C03118)。
摘 要:近年来,病毒载体介导的嵌合抗原受体(chimeric antigen receptor,CAR)细胞疗法已成为癌症治疗领域热点,并在血液系统恶性肿瘤患者中取得了显著的临床疗效,但其诱导的CAR永久表达可能导致严重不良反应。信使RNA(messenger RNA,mRNA)嵌合抗原受体疗法由于无插入性诱变和较小的靶外毒性风险,有望成为新一代更安全有效的治疗方法。该疗法通过将编码CAR的mRNA转染至效应免疫细胞中,以在体内产生免疫应答,已被应用于B细胞恶性肿瘤、淋巴瘤及急性髓细胞性白血病(acute myelogenous leukemia,AML)等多种癌症的治疗。mRNA的提纯、修饰及转染技术的不断优化,使得mRNA CAR表达更持久,杀伤效率更高,作用范围更广。全文综述了mRNA CAR的递送方式、优势及相关恶性肿瘤疗法的研究进展。In recent years,viral vector-mediated chimeric antigen receptor(CAR)cell therapy has emerged as a prominent topic in the field of cancer treatment and has demonstrated significant clinical efficacy in patients with hematological malignancies.However,the permanent expression of CAR induced by this therapy may give rise to severe adverse reactions.In contrast,messenger RNA(mRNA)chimeric antigen receptor therapy is anticipated to become a new generation of safer and more effective treatments due to its lack of insertional mutagenesis and minimal risk of off-target toxicity.This therapeutic approach involves transfecting effector immune cells with CAR-encoding mRNA to elicit an immune response within the body.It has been employed for treating B-cell malignancies,lymphoma,acute myelogenous leukemia(AML),and other cancers.The continuous optimization of mRNA purification,modification,and transfection technology enhances CAR expression durability,while increasing killing efficiency and expanding the range of action.This paper reviews the research advances on CAR-encoding mRNA delivery,its application and advantages in cancer therapies.
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