ADD bioreactor scale-up stuff

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Nathan Dwarshuis 2021-08-01 22:30:21 -04:00
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@ -747,6 +747,42 @@ compared to state-of-the-art systems.
\subsection{methods to scale T cells}
In order to scale T cell therapies to meet clinical demands, automation and
bioreactors will be necessary. To this end, there are several choices that have
found success in the clinic.
The WAVE bioreactor (GE Healthcare) is the choice of expansion for many clinical
applications [5,45,64]. It is part of a broader class of bioreactors that
consist of rocking platforms that agitate a bag filled with media and cells.
Importantly, it has built-in sensors for measuring media flow rate, carbon
dioxide, oxygen, pH, and nutrient consumption which enables automation.
Unfortunately, in some settings this is not considered scalable as only one bag
per bioreactor is allowed at once\cite{Roddie2019}.
% BACKGROUND find clinical trials (if any) that use this
Alternatively, the CliniMACS Prodigy (Miltenyi) is an all-in-one system that is
a fully closed system that removes the need for expensive cleanrooms and
associated personnel. It contains modules to perform transduction, expansion,
and washing. This setup also implies that fewer mistakes and handling errors
will be made, since many of the steps are internal to the machine. Initial
investigations have shown that it can yield T cells doses required for clinical
use.
% https://reader.elsevier.com/reader/sd/pii/S1465324917307041?token=CF7C833CF6E0A7D5E003703A845A51066D028D5BF605792595DCF8D540B23933F4B856A0A9881C6DDEFE0C38D220A768&originRegion=us-east-1&originCreation=20210802022804
At the time of writing, several clinical trial are underway which use the
CliniMACS, although mostly for stem-cell based cell treatments.
Finally, another option that has been investigated for T cell expansion is the
Grex bioreactor (Wilson Wolf). This is effectively a tall tissue-culture plate
with a porous membrane at the bottom, which allows gas exchange to the active
cell culture at the bottom of the plate while permitting large volumes of media
to be loaded on top without suffocating the cells. While this is quite similar
to plates and flasks normally used for small-scale research, the important
difference is that its larger size requires fewer interactions and keeps the
cells at a higher nutrient concentration for longer periods of time. However, it
is still a an open system and requires manual (by default) interaction from an
operator to load, feed, and harvest the cell product. Grex bioreactors have
been using to grow \glspl{til} [58] and virus-specific T cells [61].
\subsection{overview of T cell quality}
% memory