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

Matthew Li, Ling Yee Chin, Sykuri Shukor, Alfred G. Tamayo, Marcela V. Maus, Biju Parekkadan

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)102-107
Number of pages6
JournalAutoimmunity
Volume52
Issue number3
DOIs
StatePublished - Apr 3 2019

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Keywords

  • CTLA4
  • Lag3
  • PD1
  • T-cell
  • TIGIT
  • TIM3
  • biomanufacturing
  • checkpoint
  • immunotherapy

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