Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role ...Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.展开更多
针对靶向CD19的嵌合抗原受体修饰T细胞(chimeric antigen receptor T cell,CAR-T)治疗儿童和成人复发或难治性急性淋巴细胞白血病已取得满意疗效。目前,CAR-T在恶性实体瘤如胰腺癌、肺癌、恶性胸膜间皮瘤等治疗中的应用价值成为临床研...针对靶向CD19的嵌合抗原受体修饰T细胞(chimeric antigen receptor T cell,CAR-T)治疗儿童和成人复发或难治性急性淋巴细胞白血病已取得满意疗效。目前,CAR-T在恶性实体瘤如胰腺癌、肺癌、恶性胸膜间皮瘤等治疗中的应用价值成为临床研究重点。但CAR-T治疗恶性实体瘤面临诸多困难和挑战,如靶向抗原的选择、免疫抑制性肿瘤微环境以及安全性等。本文就CAR-T治疗恶性实体瘤靶向抗原选择的研究进展作一综述。展开更多
胶质母细胞瘤是成人最常见且最致命的肿瘤之一,由于其进展迅速、侵袭性强和血脑屏障的存在,胶质母细胞瘤的治疗有别于其他实体肿瘤,常规治疗预后欠佳。使用免疫疗法治疗胶质母细胞瘤的探索已经持续了几十年,效果也欠佳。但随着胶质母细...胶质母细胞瘤是成人最常见且最致命的肿瘤之一,由于其进展迅速、侵袭性强和血脑屏障的存在,胶质母细胞瘤的治疗有别于其他实体肿瘤,常规治疗预后欠佳。使用免疫疗法治疗胶质母细胞瘤的探索已经持续了几十年,效果也欠佳。但随着胶质母细胞瘤特异性抗原的研究进展、各项相关技术的发展以及早期临床试验的成功,免疫疗法又回到了人们的视线中。嵌合抗原受体T细胞(chimeric antigen receptor-modified T cell,CAR-T)治疗是一种新兴的肿瘤免疫疗法。该文回顾既往文献,总结了一些可用于CAR-T疗法治疗胶质母细胞瘤的相关抗原,并总结了CAR-T疗法治疗胶质母细胞瘤在内的实体肿瘤所面临的问题和挑战,包括肿瘤微环境中存在的T细胞耗竭、肿瘤的异质性、归巢率低等,对CAR-T疗法改进方案等进行综述。展开更多
基金supported by grants from National Natural Science Foundation of China(Nos.81870140 and 82070184)Peking University People’s Hospital Research and Development Funds(No.RDL2021-01)+1 种基金Beijing Nova Program(No.20220484235)Beijing Life Oasis Public Service Center(No.CARTFR-01)
文摘Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell therapy.Common MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and limitations.It has been well documented that MRD positivity predicts a poor prognosis and even disease relapse.Thus,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical practice.This review assesses the common and novel MRD assessment methods.In addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment effect.Furthermore,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.
文摘针对靶向CD19的嵌合抗原受体修饰T细胞(chimeric antigen receptor T cell,CAR-T)治疗儿童和成人复发或难治性急性淋巴细胞白血病已取得满意疗效。目前,CAR-T在恶性实体瘤如胰腺癌、肺癌、恶性胸膜间皮瘤等治疗中的应用价值成为临床研究重点。但CAR-T治疗恶性实体瘤面临诸多困难和挑战,如靶向抗原的选择、免疫抑制性肿瘤微环境以及安全性等。本文就CAR-T治疗恶性实体瘤靶向抗原选择的研究进展作一综述。
文摘胶质母细胞瘤是成人最常见且最致命的肿瘤之一,由于其进展迅速、侵袭性强和血脑屏障的存在,胶质母细胞瘤的治疗有别于其他实体肿瘤,常规治疗预后欠佳。使用免疫疗法治疗胶质母细胞瘤的探索已经持续了几十年,效果也欠佳。但随着胶质母细胞瘤特异性抗原的研究进展、各项相关技术的发展以及早期临床试验的成功,免疫疗法又回到了人们的视线中。嵌合抗原受体T细胞(chimeric antigen receptor-modified T cell,CAR-T)治疗是一种新兴的肿瘤免疫疗法。该文回顾既往文献,总结了一些可用于CAR-T疗法治疗胶质母细胞瘤的相关抗原,并总结了CAR-T疗法治疗胶质母细胞瘤在内的实体肿瘤所面临的问题和挑战,包括肿瘤微环境中存在的T细胞耗竭、肿瘤的异质性、归巢率低等,对CAR-T疗法改进方案等进行综述。
