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文章:

CAR-T细胞疗法监测的进展与挑战:血液恶性肿瘤参数与标志物的全面综述

Advancement and Challenges in Monitoring of CAR-T Cell Therapy: A Comprehensive Review of Parameters and Markers in Hematological Malignancies

原文发布日期:29 September 2024

DOI: 10.3390/cancers16193339

类型: Article

开放获取: 是

 

英文摘要:

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to 80% of patients following CAR-T cell therapy. CRS results from the uncontrolled overproduction of proinflammatory cytokines, which leads to symptoms such as fever, headache, hypoxia, or neurological complications. CAR-T cell detection is possible by the use of flow cytometry (FC) or quantitative polymerase chain reaction (qPCR) assays, the two primary techniques used for CAR-T evaluation in peripheral blood, bone marrow (BM), and cerebrospinal fluid (CSF). State-of-the-art imaging technologies play a crucial role in monitoring the distribution and persistence of CAR-T cells in clinical trials. Still, they can also be extended with the use of FC and digital PCR (dPCR). Monitoring the changes in cell populations during disease progression and treatment gives an important insight into how the response to CAR-T cell therapy develops on a cellular level. It can help improve the therapeutic design and optimize CAR-T cell therapy to make it more precise and personalized, which is crucial to overcoming the problem of tumor relapse.

 

摘要翻译: 

嵌合抗原受体T细胞(CAR-T)疗法已彻底改变了复发/难治性B细胞淋巴瘤的治疗。尽管该疗法取得了成功,但其伴随的不良事件发生率较高,包括细胞因子释放综合征(CRS)、免疫效应细胞相关神经毒性综合征(ICANS)或血细胞减少症,在接受CAR-T细胞治疗的患者中发生率甚至高达80%。CRS源于促炎细胞因子的失控性过度产生,导致发热、头痛、低氧或神经系统并发症等症状。通过流式细胞术(FC)或定量聚合酶链反应(qPCR)检测可实现CAR-T细胞的监测,这两种技术是评估外周血、骨髓(BM)和脑脊液(CSF)中CAR-T细胞的主要方法。前沿影像技术在临床试验中对监测CAR-T细胞的分布与存续起着关键作用,同时也可结合流式细胞术和数字PCR(dPCR)进行扩展应用。通过监测疾病进展和治疗过程中细胞群的变化,能够从细胞层面深入理解CAR-T细胞治疗的应答机制,有助于优化治疗方案设计,推动CAR-T细胞疗法向更精准化、个体化方向发展,这对克服肿瘤复发难题具有重要意义。

 

原文链接:

Advancement and Challenges in Monitoring of CAR-T Cell Therapy: A Comprehensive Review of Parameters and Markers in Hematological Malignancies

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