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血液系统恶性肿瘤 CAR-T 治疗后复发的临床决定因素:联合主动策略以克服治疗局限性

英文原题:Clinical determinants of relapse following CAR-T therapy for hematologic malignancies: Coupling active strategies to overcome therapeutic limitations.

查看英文原题

Clinical determinants of relapse following CAR-T therapy for hematologic malignancies: Coupling active strategies to overcome therapeutic limitations.

PubMed 2021/11/09(内容时间) Curr Res Transl Med Q3 · IF 3(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)-T细胞疗法的出现被誉为治疗B细胞急性淋巴细胞白血病(B-ALL)和弥漫性大B细胞淋巴瘤(DLBCL)的重大突破。尽管多项有前景的CAR-T 细胞临床试验持续获得FDA和中国临床试验注册中心(ChiCTR)的批准,但许多血液系统恶性肿瘤患者仍因基因突变、抗原逃逸、谱系转换、CAR-T 细胞持久性差、CAR-T 细胞耗竭以及针对CAR-T 细胞的免疫原性而在治疗后出现疾病复发。本文总结了CAR构建体的结构特征,并讨论了已知与CAR-T 细胞治疗后复发相关的临床因素。通过更好地理解此类疾病复发的机制基础,未来将有可能充分发挥这一强效治疗模式的潜力。本综述将聚焦于当前旨在克服CAR-T 细胞疗法已知局限性的激活策略,以努力改善血液系统恶性肿瘤患者的预后。

展开英文摘要原文

The advent of chimeric antigen receptor (CAR)-T cell therapy has been hailed as a major breakthrough in the treatment of B cell acute lymphoblastic leukemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). While multiple promising CAR-T cell clinical trials continue to receive approval from the FDA and the Chinese Clinical Trial Register (ChiCTR), many hematologic malignancies patients nonetheless experience disease relapse following treatment as a consequence of genetic mutations, antigen escape, lineage switching, poor CAR-T cell persistence, CAR T cell exhaustion, and immunogenicity against CAR T cells.

In this article, we summarize the structural characteristics of CAR constructs and discuss clinical factors known to be related to relapse following CAR-T cell treatment. By better understanding the mechanistic basis for such disease recurrence, it will be possible to fully realize the potential of this potent therapeutic modality in the future. This review will focus on current activate strategies aimed at overcoming known limitations to CAR-T cell therapy in an effort to improve hematologic malignancies patient outcomes.

论文信息

作者
Wang L
文献类型
综述
期刊
Current research in translational medicine2022 Jan
原文标识
PubMed 34768218 · DOI 10.1016/j.retram.2021.103320