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Closed loop bioreactor system for the ex vivo expansion of human T cells
Authors:MATTHEW LI  LING-YEE CHIN  SYUKRI SHUKOR  ALFRED TAMAYO  MARCELA V MAUS  BIJU PAREKKADAN
Institution:1. Center for Surgery, Innovation, and Bioengineering, Department of Surgery, Massachusetts General Hospital and the Shriners Hospitals for Children, Boston, Massachusetts, USA;2. Harvard Medical School, Boston, Massachusetts, USA;3. Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA;4. Harvard Stem Cell Institute, Cambridge, Massachusetts, USA;5. Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, USA
Abstract:

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:biomanufacturing  bioreactors  immunotherapy  T cells
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