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在自动化细胞处理器上制造嵌合抗原受体T细胞
在自动化细胞处理器上制造嵌合抗原受体T细胞
JoVE Journal
Medicine
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JoVE Journal Medicine
Chimeric Antigen Receptor T Cell Manufacturing on an Automated Cell Processor

在自动化细胞处理器上制造嵌合抗原受体T细胞

Full Text
3,858 Views
06:18 min
August 18, 2023

DOI: 10.3791/65488-v

Rene Machietto1, Nicholas Giacobbe1, Jessica Perazzelli2, Ted J. Hofmann2, Allison Barz Leahy2,3, Stephan A. Grupp1,2,3, Yongping Wang1,3,4, Stephan Kadauke1,3,4

1Cell and Gene Therapy Laboratory, Department of Pathology and Laboratory Medicine,Children’s Hospital of Philadelphia, 2Division of Oncology, Department of Pediatrics,Children’s Hospital of Philadelphia, 3Perelman School of Medicine at the University of Pennsylvania, 4Division of Transfusion Medicine, Department of Pathology and Laboratory Medicine,Children’s Hospital of Philadelphia

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Overview

This article details a semi-automated process for manufacturing chimeric antigen receptor T cells (CAR T-cells) for clinical use. The method utilizes an automated cell processor for viral transduction and cultivation, offering flexibility and cost-effectiveness compared to commercial alternatives.

Key Study Components

Area of Science

  • Cell and gene therapy
  • Immunotherapy
  • Clinical trial methodology

Background

  • Chimeric antigen receptor T cells are a promising treatment for various cancers.
  • Manufacturing CAR T-cells traditionally involves complex, labor-intensive processes.
  • Automation can enhance efficiency and reduce costs in cell production.
  • Closed systems are essential for maintaining sterility and safety in clinical applications.

Purpose of Study

  • To present a protocol for the semi-automated production of CAR T-cells.
  • To identify potential pitfalls in the process development for clinical trials.
  • To explore the adaptability of the method for other cell and gene therapies.

Methods Used

  • Utilization of an automated cell processor for T-cell cultivation.
  • Viral transduction to introduce CAR genes into T-cells.
  • Customization of protocols through computer control.
  • Implementation in a closed system to ensure sterility.

Main Results

  • The protocol allows for the production of clinical-grade CAR T-cells at lower costs.
  • Flexibility in protocol customization enhances usability in various settings.
  • The method can be adapted for CAR T-cells targeting different antigens.
  • Potential for broader applications in other cell and gene therapies.

Conclusions

  • The semi-automated process is a viable alternative to traditional CAR T-cell manufacturing.
  • Cost-effectiveness and adaptability are significant advantages of this method.
  • Further exploration of additional CAR T-cell targets and gene therapies is warranted.

Frequently Asked Questions

What are chimeric antigen receptor T cells?
Chimeric antigen receptor T cells are genetically modified T cells designed to target and kill cancer cells.
How does the automated cell processor work?
The automated cell processor performs viral transduction and cultivation of T cells in a controlled environment.
What are the benefits of using a closed system?
A closed system helps maintain sterility and reduces the risk of contamination during the manufacturing process.
Can this process be adapted for other therapies?
Yes, the protocol can be customized for other CAR T-cell targets and various cell and gene therapies.
What are the cost implications of this method?
This method allows for the production of clinical-grade CAR T-cells at significantly lower costs compared to commercial options.
What challenges might arise during implementation?
Potential pitfalls include ensuring protocol customization and maintaining compliance with clinical trial regulations.

本文详细介绍了临床使用的嵌合抗原受体T细胞的制造过程,特别是使用能够进行病毒转导和T细胞培养的自动化细胞处理器。我们提供建议并描述在早期临床试验的工艺开发和实施过程中应考虑的陷阱。

我们协议的优点是它是一个半自动化的封闭系统,仍然提供灵活性。劳动密集型步骤被自动化所取代,自动化由计算机运行,并且由于它由计算机运行,因此用户可以自定义其协议。这也是在一个封闭的系统中完成的。

我们发现,医院中常见的干细胞实验室能够以比商业替代品低得多的成本生产临床级CAR-T细胞。我们认为,我们的工艺可以很容易地用于使CAR-T细胞对其他靶点具有特异性,也可以用于制造其他类型的细胞和基因疗法。我们的团队准备探索其他CAR-T细胞靶点和新的基因疗法。

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嵌合抗原受体T细胞 CAR-T细胞 免疫疗法 自动化细胞处理器 CliniMACS神童 细胞治疗生产 封闭系统 污染风险 T细胞转导 病毒载体 CD4+/CD8+ T细胞富集 活化 扩增 收获 活性基质 定制 药品生产质量管理规范(cGMP) 研究性新药(IND) 放行测试

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