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BCMA CAR-T 治疗的创新:超越 Model T 的构建

英文原题:Innovation in BCMA CAR-T therapy: Building beyond the Model T.

查看英文原题

Innovation in BCMA CAR-T therapy: Building beyond the Model T.

PubMed 2022/11/24(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

靶向B细胞成熟抗原(BCMA)的自体CAR-T 细胞疗法彻底改变了多发性骨髓瘤领域,就如同一个世纪前福特T型车彻底改变了最初的汽车世界一样。

然而,我们才刚刚开始理解如何提高这些细胞疗法的疗效和可用性。在这篇综述中,我们以三个汽车类比来探讨BCMA CAR-T 疗法的创新方向:更强的引擎、更好的里程和无忧的交付。首先,我们可以在BCMA靶向方面构建更强的引擎:改善抗原结合、调节抗原密度的工具,以及更好地触及抗原本身的装甲化改造。其次,我们可以通过体外CAR设计和体内免疫操控来提高应答持久性方面的“里程”。第三,我们可以通过快速生产方案和现货产品来实现无忧交付。正如100多年前T型车为汽车制造设定了标杆一样,idecabtagene vicleucel和ciltacabtagene autoleucel的获批现已为BCMA CAR-T 疗法设定了起点。与任何新兴技术一样,无论是汽车还是细胞,最好的创新和优化尚未到来。

展开英文摘要原文

Autologous chimeric antigen receptor T-cell (CAR-T) therapies targeting B-cell maturation antigen (BCMA) have revolutionized the field of multiple myeloma in the same way that the Ford Model T revolutionized the original CAR world a century ago.

However, we are only beginning to understand how to improve the efficacy and usability of these cellular therapies. In this review, we explore three automotive analogies for innovation with BCMA CAR-T therapies: stronger engines, better mileage, and hassle-free delivery. Firstly, we can build stronger engines in terms of BCMA targeting: improved antigen binding, tools to modulate antigen density, and armoring to better reach the antigen itself.

Secondly, we can improve "mileage" in terms of response durability through ex vivo CAR design and in vivo immune manipulation. Thirdly, we can implement hassle-free delivery through rapid manufacturing protocols and off-the-shelf products.

Just as the Model T set a benchmark for car manufacturing over 100 years ago, idecabtagene vicleucel and ciltacabtagene autoleucel have now set the starting point for BCMA CAR-T therapy with their approvals. As with any emerging technology, whether automotive or cellular, the best in innovation and optimization is yet to come.

论文信息

作者
Banerjee R、Lee SS、Cowan AJ
单位
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, United States.United States
文献类型
综述
期刊
Frontiers in oncology2022
原文标识
PubMed 36505779 · DOI 10.3389/fonc.2022.1070353