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多发性骨髓瘤的嵌合抗原受体(CAR)T 细胞治疗

英文原题:Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.

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Chimeric antigen receptor (CAR) T-cell therapy for multiple myeloma.

PubMed 2021/09/25(内容时间) Pharmacol Ther Q1 · IF 13.5(JCR 2025)

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中文摘要

尽管过去二十年多发性骨髓瘤患者的治疗结局显著改善,骨髓瘤仍是一种不可治愈的疾病。治疗多发性骨髓瘤的新型免疫疗法不断涌现,包括单克隆抗体、抗体药物偶联物、双特异性抗体和嵌合抗原受体(CAR)T细胞疗法。在重度预处理骨髓瘤患者中令人瞩目的缓解率和临床疗效促成了FDA于2021年3月批准首个骨髓瘤CAR-T 疗法。在骨髓瘤CAR-T 疗法的众多不同靶点中,B细胞成熟抗原(BCMA)是迄今为止最成功的靶点,但其他可用于单靶点或双靶点CAR-T 的靶点正在积极探索中。本文介绍了当前骨髓瘤CAR-T 疗法的临床疗效和安全性。导致耐药的潜在机制包括CAR-T 细胞清除、抗原逃逸和免疫抑制性肿瘤微环境。增强骨髓瘤CAR-T 的新策略也将予以描述。在本文中,我们全面综述了骨髓瘤CAR-T 疗法的当前数据和未来方向。

展开英文摘要原文

Although treatment outcomes of multiple myeloma patients have improved significantly during the last two decades, myeloma is still an incurable disease. There are newly emerging immunotherapies to treat multiple myeloma including monoclonal antibodies, antibody-drug conjugate, bispecific antibodies, and chimeric antigen receptor (CAR) T cell therapy. Impressive response rate and clinical efficacy in heavily pretreated myeloma patients led to the FDA approval of the first myeloma CAR-T therapy in March 2021.

Among many different targets for myeloma CAR-T therapies, B Cell Maturation Antigen (BCMA) has been the most successful target so far, but other targets which can be used either for single-target or dual-target CAR-T's are actively being explored. Clinical efficacy and safety of current myeloma CAR-T therapies will be presented here.

Potential mechanisms leading to resistance include clearance of CAR-T cells, antigenic escape, and immunosuppressive tumor microenvironment. Novel strategies to enhance myeloma CAR-T will also be described. In this article, we provide a comprehensive review of the current data and the future directions of myeloma CAR-T therapies.

论文信息

作者
Choi T、Kang Y
第一作者单位
Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA.United States
通讯作者单位
Division of Hematologic Malignancies and Cellular Therapy, Duke University Medical Center, Durham, NC, USA. Electronic address: yubin.kang@duke.edu.United States
文献类型
美国 NIH 资助研究 · 综述
期刊
Pharmacology & therapeutics2022 Apr
原文标识
PubMed 34582835 · DOI 10.1016/j.pharmthera.2021.108007