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核心技术专利:CN118964589B侵权必究
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原代T细胞的白光光谱特征与增殖动态行为:在线、实时且无需采样的嵌合抗原受体T细胞生产监测的可能性

White Light Spectroscopy Characteristics and Expansion Dynamic Behavior of Primary T-Cells: A Possibility of Online, Real-Time, and Sampling-Less CAR T-Cell Production Monitoring.

作者信息

Wacogne Bruno, Brito Maxime, Gamonet Clémentine, Rouleau Alain, Frelet-Barrand Annie

机构信息

CNRS, Institut FEMTO-ST, Université Marie et Louis Pasteur, 25000 Besançon, France.

Centre Hospitalier Universitaire de Besançon, Centre d'Investigation Clinique, INSERM CIC 1431, 25030 Besançon, France.

出版信息

Biosensors (Basel). 2025 Apr 15;15(4):251. doi: 10.3390/bios15040251.


DOI:10.3390/bios15040251
PMID:40277564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12025026/
Abstract

The production of advanced therapy medicinal products (ATMP) is a long and highly technical process, resulting in a high cost per dose, which reduces the number of eligible patients. There is a critical need for a closed and sample-free monitoring system to perform the numerous quality controls required. Current monitoring methods are not optimal, mainly because they require the system to be opened up for sampling and result in material losses. White light spectroscopy has emerged as a technique for sample-free control compatible with closed systems. We have recently proposed its use to monitor cultures of CEM-C1 cell lines. In this paper, we apply this method to T-cells isolated from healthy donor blood samples. The main differences between cell lines and human primary T-cells lie in the slightly different shape of their absorption spectra and in the dynamics of cell expansion. T-cells do not multiply exponentially, resulting in a non-constant generation time. Cell expansion is described by a power-law model, which allows for the definition of instantaneous generation times. A correlation between the linear asymptotic behavior of these generation times and the initial cell concentration leads to the hypothesis that this could be an early predictive marker of the final culture concentration. To the best of our knowledge, this is the first time that such concepts have been proposed.

摘要

先进治疗药品(ATMP)的生产是一个漫长且技术要求很高的过程,导致每剂成本高昂,这减少了符合条件的患者数量。迫切需要一个封闭且无需取样的监测系统来进行所需的众多质量控制。当前的监测方法并非最佳,主要是因为它们需要打开系统进行取样并导致材料损失。白光光谱法已成为一种与封闭系统兼容的无需取样的控制技术。我们最近提议将其用于监测CEM - C1细胞系的培养。在本文中,我们将此方法应用于从健康供体血样中分离出的T细胞。细胞系与人类原代T细胞之间的主要差异在于它们吸收光谱的形状略有不同以及细胞扩增的动力学。T细胞不会呈指数增殖,导致世代时间不恒定。细胞扩增由幂律模型描述,该模型允许定义瞬时世代时间。这些世代时间的线性渐近行为与初始细胞浓度之间的相关性导致这样一种假设,即这可能是最终培养浓度的早期预测指标。据我们所知,这是首次提出此类概念。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f1300792b483/biosensors-15-00251-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f685e737bc3a/biosensors-15-00251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/fd7bb0b782ec/biosensors-15-00251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/1be7a41087e4/biosensors-15-00251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f66e2fca9a49/biosensors-15-00251-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/2356504cd135/biosensors-15-00251-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/0523b682ea35/biosensors-15-00251-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/230729b08a7a/biosensors-15-00251-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/a590be272628/biosensors-15-00251-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/d8431e569d45/biosensors-15-00251-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/6437ee825a34/biosensors-15-00251-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f1300792b483/biosensors-15-00251-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f685e737bc3a/biosensors-15-00251-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/fd7bb0b782ec/biosensors-15-00251-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/1be7a41087e4/biosensors-15-00251-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f66e2fca9a49/biosensors-15-00251-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/2356504cd135/biosensors-15-00251-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/0523b682ea35/biosensors-15-00251-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/230729b08a7a/biosensors-15-00251-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/a590be272628/biosensors-15-00251-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/d8431e569d45/biosensors-15-00251-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/6437ee825a34/biosensors-15-00251-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6f2e/12025026/f1300792b483/biosensors-15-00251-g011.jpg

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White Light Spectroscopy Characteristics and Expansion Dynamic Behavior of Primary T-Cells: A Possibility of Online, Real-Time, and Sampling-Less CAR T-Cell Production Monitoring.

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引用本文的文献

[1]
White Light Spectroscopy for Sampling-Free Bacterial Contamination Detection During CAR T-Cells Production: Towards an On-Line and Real-Time System.

Biosensors (Basel). 2025-8-6

本文引用的文献

[1]
Integration of ζ-deficient CARs into the CD3ζ gene conveys potent cytotoxicity in T and NK cells.

Blood. 2024-6-20

[2]
CAR-T cell therapy: Where are we now, and where are we heading?

Blood Sci. 2023-11-2

[3]
Absorption/Attenuation Spectral Description of ESKAPEE Bacteria: Application to Seeder-Free Culture Monitoring, Mammalian T-Cell and Bacteria Mixture Analysis and Contamination Description.

Sensors (Basel). 2023-4-27

[4]
Cell Immortalization: In Vivo Molecular Bases and In Vitro Techniques for Obtention.

BioTech (Basel). 2023-1-28

[5]
CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans.

Curr Res Transl Med. 2023

[6]
Absorption Spectra Description for T-Cell Concentrations Determination and Simultaneous Measurements of Species during Co-Cultures.

Sensors (Basel). 2022-11-27

[7]
Umbilical Cord Blood as a Source of Less Differentiated T Cells to Produce CD123 CAR-T Cells.

Cancers (Basel). 2022-6-28

[8]
Modified Manufacturing Process Modulates CD19CAR T-cell Engraftment Fitness and Leukemia-Free Survival in Pediatric and Young Adult Subjects.

Cancer Immunol Res. 2022-7-1

[9]
Paper-based plasmonic substrates as surface-enhanced Raman scattering spectroscopy platforms for cell culture applications.

Mater Today Bio. 2021-8-4

[10]
Improving outcomes and mitigating costs associated with CAR T-cell therapy.

Am J Manag Care. 2021-8

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