急性B淋巴细胞白血病CD19 CAR-T细胞治疗后阳性复发的机制和挽救性治疗策略  

The mechanisms and salvage treatment strategies underlying positive relapse following CD19 CAR-T celltherapyinB-acutelymphoblasticleukemia

作　　者：卢聪[1] 徐佳 梅恒[1] Lu Cong;Xu Jia;Mei Heng(Institute of Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Hubei Clinical Medical Center of Cell Therapy for Neoplastic Disease,Wuhan 430022,China)

机构地区：[1]华中科技大学同济医学院附属协和医院血液科,湖北省肿瘤疾病细胞治疗临床医学研究中心,武汉430022

出　　处：《中华血液学杂志》2024年第10期970-976,共7页Chinese Journal of Hematology

基　　金：国家自然科学基金(82330005)。

摘　　要：尽管嵌合抗原受体T(CAR-T)细胞疗法改变了复发/难治急性B淋巴细胞白血病(R/R B-ALL)的治疗格局,仍然有50%患者在治疗后1年内复发,且60%左右为阳性复发。导致CAR-T细胞治疗复发的机制主要与肿瘤异质性、CAR-T细胞自身功能障碍和体内扩增及持续性不佳以及抑制性免疫微环境相关。这篇综述旨在探讨改善CAR-T治疗后复发或进展患者结局的挽救性策略,包括同一靶点二次CAR-T细胞治疗或者更换靶点回输,联合免疫检查点抑制剂,新型靶向药物包括新型单克隆抗体、抗体药物偶联物以及双特异性抗体等应用,使用小分子化合物逆转CAR-T耐药等,阐述了可能的相关机制并列举了相关的临床资料。经过对患者CAR-T治疗失败后的复杂情况探讨,我们认为,这些药物在用于复发时的挽救性治疗、CAR-T治疗后维持治疗或在CAR-T细胞回输前或者回输时联合治疗时,在一定程度上可减少阳性复发或克服耐药,但改善患者的长期生存仍然面临巨大挑战。Approximately y 50%of patients suffering from relapsed/refractory B-acute lymphoblastic leukemia(R/R B-ALL),experience relapse within one year,with around 60%of these relapses being antigen-positive,despite the transformative impact of chimeric antigen receptor(CAR)T cell therapy.The mechanisms underlying relapse are primarily associated with tumor heterogeneity,CAR-T cell dysfunction,subopimal in vivo expansion and persistence,and an inhibitory immune microenvironment.This review aims to investigate salvage strategies designed to enhance outcomes for patients undergoing relapse or disease progression following the CAR-T cell therapy.These strategies include a second CAR-T cell infusion that targets either the same antigen or an alternative target,the administration of immune checkpoint inhibitors,and the utilization of novel targeted therapies including monoclonal antibodies,antibody-conjugated drugs and small molecule compounds aimed at mitigating CD19-positive relapse or overcoming CAR-T cell resistance.Nevertheless,achieving improved long-term survival for these patients continues be challenging.

关 键 词：双特异性抗体 免疫检查点抑制剂 嵌合抗原受体 长期生存 肿瘤异质性 免疫微环境 维持治疗 治疗失败 

分 类 号：R733.71[医药卫生—肿瘤]