Matthew Li1, Ling-Yee Chin1, Sykuri Shukor1, Alfred G Tamayo1, Marcela V Maus2,3, Biju Parekkadan1,4,5. 1. a Department of Surgery, Center for Surgery, Innovation, and Bioengineering, Massachusetts General Hospital , Harvard Medical School and the Shriners Hospitals for Children , Boston , M A , USA. 2. b Cancer Center , Massachusetts General Hospital , Boston , M A , USA. 3. c Harvard Medical School , Boston , M A , USA. 4. d Harvard Stem Cell Institute , Cambridge , M A , USA. 5. e Department of Biomedical Engineering , Rutgers University , Piscataway , NJ , USA.
Abstract
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.
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.
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