通过过程内细胞内质谱法对 T 细胞激活进行早期检测和代谢途径鉴定。
Early detection and metabolic pathway identification of T cell activation by in-process intracellular mass spectrometry.
机构信息
The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia, USA; National Science Foundation Engineering Research Center (ERC) for Cell Manufacturing Technologies (CMaT), Atlanta, Georgia, USA.
Marcus Center for Therapeutic Cell Characterization and Manufacturing, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA.
出版信息
Cytotherapy. 2023 Sep;25(9):1006-1015. doi: 10.1016/j.jcyt.2023.03.010. Epub 2023 Apr 13.
BACKGROUND AIMS
In-process monitoring and control of biomanufacturing workflows remains a significant challenge in the development, production, and application of cell therapies. New process analytical technologies must be developed to identify and control the critical process parameters that govern ex vivo cell growth and differentiation to ensure consistent and predictable safety, efficacy, and potency of clinical products.
METHODS
This study demonstrates a new platform for at-line intracellular analysis of T-cells. Untargeted mass spectrometry analyses via the platform are correlated to conventional methods of T-cell assessment.
RESULTS
Spectral markers and metabolic pathways correlated with T-cell activation and differentiation are detected at early time points via rapid, label-free metabolic measurements from a minimal number of cells as enabled by the platform. This is achieved while reducing the analytical time and resources as compared to conventional methods of T-cell assessment.
CONCLUSIONS
In addition to opportunities for fundamental insight into the dynamics of T-cell processes, this work highlights the potential of in-process monitoring and dynamic feedback control strategies via metabolic modulation to drive T-cell activation, proliferation, and differentiation throughout biomanufacturing.
背景目的
在细胞治疗的开发、生产和应用中，生物制造工作流程的过程监测和控制仍然是一个重大挑战。必须开发新的过程分析技术，以识别和控制控制体外细胞生长和分化的关键过程参数，以确保临床产品的安全性、有效性和效力始终保持一致且可预测。
方法
本研究展示了一种用于 T 细胞在线内分析的新平台。通过该平台进行的非靶向质谱分析与 T 细胞评估的常规方法相关联。
结果
通过该平台从尽可能少的细胞中进行快速、无标记的代谢测量，可以在早期检测到与 T 细胞激活和分化相关的光谱标记物和代谢途径。与 T 细胞评估的常规方法相比，这可以减少分析时间和资源。
结论
除了有机会深入了解 T 细胞过程的动态之外，这项工作还强调了通过代谢调节进行过程监测和动态反馈控制策略的潜力，以在整个生物制造过程中驱动 T 细胞的激活、增殖和分化。
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