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Effects of intermittent T-cell cluster disaggregation on proliferative capacity and checkpoint marker expression.
Autoimmunity ( IF 3.5 ) Pub Date : 2019-06-25 , DOI: 10.1080/08916934.2019.1630064
Matthew Li 1 , Ling-Yee Chin 1 , Sykuri Shukor 1 , Alfred G Tamayo 1 , Marcela V Maus 2, 3 , Biju Parekkadan 1, 4, 5
Affiliation  

Background/aim: T-cell immunotherapies are rapidly gaining grounds in clinical success. Presently, there is first-to-market knowledge on the translation of research scale methods to clinical and commercial scales. Improved understanding can lead to more consistent and efficient production, scaling, and eventual potency. T-cell checkpoint markers, proliferation, and T-cell cluster size and disaggregation are one set of parameters that have yet to be explored. Methods: We herein activated T-cells and assessed various mechanical dissociation frequencies in relation to expression of checkpoint markers (measured by flow cytometry). Results: We herein find increased T-cell proliferation capacity with increased dissociation frequency. We also find that with increased cluster size and duration, lower proliferation, and increased expression of checkpoint markers. Conclusions: These findings reveal new translation findings with respect to T-cell handling and production and suggest that T-cell disaggregation may be important to improved cell yields and phenotype.

中文翻译:

间歇性T细胞簇解聚对增殖能力和检查点标记表达的影响。

背景/目的:T细胞免疫疗法在临床成功中迅速获得发展。目前,在将研究规模方法转换为临床和商业规模方面,已有首批上市知识。更好的理解可以导致更一致,更有效的生产,扩展和最终的效能。T细胞检查点标记,增殖以及T细胞簇的大小和分解是尚未探索的一组参数。方法:我们在此激活了T细胞,并评估了与检查点标志物表达有关的各种机械解离频率(通过流式细胞仪测量)。结果:我们在本文中发现随着解离频率增加,T细胞增殖能力增加。我们还发现,随着簇的大小和持续时间的增加,增殖降低,并增加了检查点标记的表达。结论:这些发现揭示了有关T细胞处理和生产的新翻译发现,并暗示T细胞分解可能对提高细胞产量和表型很重要。
更新日期:2019-11-01
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