Effects of intermittent T-cell cluster disaggregation on proliferative capacity and checkpoint marker expression

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,...

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Main Authors: Matthew Li (Author), Ling-Yee Chin (Author), Sykuri Shukor (Author), Alfred G. Tamayo (Author), Marcela V. Maus (Author), Biju Parekkadan (Author)
Format: Book
Published: Taylor & Francis Group, 2019-04-01T00:00:00Z.
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Summary: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.
Item Description:0891-6934
1607-842X
10.1080/08916934.2019.1630064