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