From 7047f20a247e9199d86f9c4f8b6ffae794094150 Mon Sep 17 00:00:00 2001 From: ndwarshuis Date: Sun, 1 Aug 2021 22:30:21 -0400 Subject: [PATCH] ADD bioreactor scale-up stuff --- tex/thesis.tex | 36 ++++++++++++++++++++++++++++++++++++ 1 file changed, 36 insertions(+) diff --git a/tex/thesis.tex b/tex/thesis.tex index 8d6db56..eced960 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -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