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嵌合抗原受体T细胞疗法治疗急性淋巴细胞白血病的挑战与临床策略:综述与进展

Challenges and Clinical Strategies of CAR T-Cell Therapy for Acute Lymphoblastic Leukemia: Overview and Developments.

作者信息

Xu Xinjie, Huang Shengkang, Xiao Xinyi, Sun Qihang, Liang Xiaoqian, Chen Sifei, Zhao Zijing, Huo Zhaochang, Tu Sanfang, Li Yuhua

机构信息

Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

出版信息

Front Immunol. 2021 Feb 10;11:569117. doi: 10.3389/fimmu.2020.569117. eCollection 2020.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy exhibits desirable and robust efficacy in patients with acute lymphoblastic leukemia (ALL). Stimulated by the revolutionized progress in the use of FDA-approved CD19 CAR T cells, novel agents with CAR designs and targets are being produced in pursuit of superior performance. However, on the path from bench to bedside, new challenges emerge. Accessibility is considered the initial barrier to the transformation of this patient-specific product into a commercially available product. To ensure infusion safety, profound comprehension of adverse events and proactive intervention are required. Additionally, resistance and relapse are the most critical and intractable issues in CAR T-cell therapy for ALL, thus precluding its further development. Understanding the limitations through up-to-date insights and characterizing multiple strategies will be critical to leverage CAR T-cell therapy flexibly for use in clinical situations. Herein, we provide an overview of the application of CAR T-cell therapy in ALL, emphasizing the main challenges and potential clinical strategies in an effort to promote a standardized set of treatment paradigms for ALL.

摘要

嵌合抗原受体(CAR)T细胞疗法在急性淋巴细胞白血病(ALL)患者中展现出了理想且强大的疗效。受到FDA批准的CD19 CAR T细胞使用方面的革命性进展的刺激,正在研发具有CAR设计和靶点的新型药物,以追求更卓越的性能。然而,在从实验室到临床应用的过程中,新的挑战也随之出现。可及性被认为是将这种针对患者的产品转化为商业可用产品的首要障碍。为确保输注安全,需要深入了解不良事件并进行积极干预。此外,耐药性和复发是CAR T细胞疗法治疗ALL时最关键且棘手的问题,因此阻碍了其进一步发展。通过最新的见解了解这些局限性并明确多种策略,对于灵活利用CAR T细胞疗法用于临床情况至关重要。在此,我们概述了CAR T细胞疗法在ALL中的应用,强调主要挑战和潜在的临床策略,以期推动一套针对ALL的标准化治疗模式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a52a/7902522/f38f86cac982/fimmu-11-569117-g001.jpg

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