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电容技术实现 CAR-T 细胞搅拌罐生物反应器培养的自动化补料、改善扩增与更高通量

英文原题:Capacitance Technology Enables Automated Feeding, Improved Expansion, and Higher Throughput of CAR-T Cell Stirred-Tank Bioreactor Cultures.

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Capacitance Technology Enables Automated Feeding, Improved Expansion, and Higher Throughput of CAR-T Cell Stirred-Tank Bioreactor Cultures.

PubMed 2026/04/01(内容时间) Biotechnol J Q2 · IF 3.7(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞为治疗某些血液系统恶性肿瘤提供了一种新颖且具有变革性的方法。然而,CAR-T 细胞的扩增方法仍在开发中,并且通常依赖于手动、低控制度的培养方法。向生物反应器的过渡将实现更高的过程控制和可扩展性,是该领域研究的重点。尽管如此,目前很少有方法能够在不进行手动细胞取样的情况下确定培养进程,而手动取样存在引入误差和增加污染风险的问题。在本文中,我们通过比较T细胞和CAR-T 细胞生物工艺与中国仓鼠卵巢(CHO)培养——后者在生物技术中广泛使用且已有成熟的电容应用——评估了电容技术是否能够提供可靠的在线细胞浓度。发现电容技术能够准确测量CAR-T 细胞浓度后,我们随后展示了使用电容衍生触发器实现补料自动化,这在细胞浓度和通量方面改善了生物工艺性能。

我们预期本研究将拓展关于电容作为合适的过程分析技术(PAT)的研究途径,以实现对CAR-T 细胞制造以及潜在其他细胞和基因治疗产品的监测和控制。它还可能实现多个批次的远程监测、收获控制以及生成大量过程数据用于建模,这将进一步推动该领域的发展。

展开英文摘要原文

Chimeric antigen receptor (CAR) T cells present a novel and transformative approach to treat certain haematological malignancies.

However, CAR-T cell expansion methods are still under development and often rely on manual, low-control culture methods. The transition to bioreactors would allow for greater process control and scalability and is a key focus of research in the field. Despite this, there are few methods to determine culture progression without the need for manual cell sampling which risks introducing errors and heightening contamination risks.

In this article, we assessed whether capacitance technology could deliver reliable, on-line cell concentrations by comparing T cell, and CAR-T cell bioprocesses with Chinese hamster ovary (CHO) cultures-widely used in biotechnology and with established capacitance usage. Finding that capacitance technology could accurately measure CAR-T cell concentrations, we then demonstrated the automation of feeding using capacitance-derived triggers which improved bioprocess performance in terms of cell concentration and throughput.

We anticipate that this study will expand avenues of investigation regarding capacitance as a suitable process analytical technology (PAT) to enable monitoring and control of CAR-T cell manufacture, and potentially other cell and gene therapy products. It may also enable remote monitoring of multiple batches, harvest control, and the generation of large collections of process data for modelling, which will further progress the field.

论文信息

作者
Colao IL、Cunningham J、Lee M、Goldrick S、Rafiq QA
单位
Department of Biochemical Engineering, University College London, London, UK.United Kingdom
期刊
Biotechnology journal2026 Apr
原文标识
PubMed 42003448 · DOI 10.1002/biot.70226