Closed loop bioreactor system for the ex vivo expansion of human T cells

Cytotherapy. 2019 Jan;21(1):76-82. doi: 10.1016/j.jcyt.2018.10.009. Epub 2018 Nov 27.


Background aim: Translation of therapeutic cell therapies to clinical-scale products is critical to realizing widespread success. Currently, however, there are limited tools that are accessible at the research level and readily scalable to clinical-scale needs.

Methods: We herein developed and assessed a closed loop bioreactor system in which (i) a highly gas-permeable silicone material was used to fabricate cell culture bags and (ii) dynamic flow was introduced to allow for dissociation of activated T-cell aggregates.

Results: Using this system, we find superior T-cell proliferation compared with conventional bag materials and flasks, especially at later time points. Furthermore, intermittent dynamic flow could easily break apart T-cell clusters.

Conclusions: Our novel closed loop bioreactor system is amenable to enhanced T-cell proliferation and has broader implications for being easily scaled for use in larger need settings.

Keywords: T cells; biomanufacturing; bioreactors; immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Batch Cell Culture Techniques / methods*
  • Bioreactors*
  • Cell Aggregation
  • Cell Proliferation / physiology*
  • Humans
  • Lymphocyte Activation
  • Permeability
  • Silicones / chemistry
  • T-Lymphocytes / physiology*


  • Silicones