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ENH proof summary section

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Nathan Dwarshuis 2021-09-07 21:15:46 -04:00
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@ -572,23 +572,23 @@ approved T cell expansion technologies involve \acd{3} and \acd{28} \glspl{mab},
usually mounted on magnetic beads. This method fails to recapitulate many key usually mounted on magnetic beads. This method fails to recapitulate many key
signals found \invivo{} and is also heavily licensed by a few companies, signals found \invivo{} and is also heavily licensed by a few companies,
limiting its long-term usefulness to manufactures and clinicians. Furthermore, limiting its long-term usefulness to manufactures and clinicians. Furthermore,
highly potent anti-tumor T cells are generally less-differentiated subtypes such highly potent, anti-tumor T cells are generally less-differentiated subtypes
as \acrlongpl{tcm} and \acrlongpl{tscm}. Despite this understanding, little has such as \acrlongpl{tcm} and \acrlongpl{tscm}. Despite this understanding, little
been done to optimize T cell expansion for generating these subtypes, including has been done to optimize T cell expansion for generating these subtypes,
measurement and feedback control strategies that are necessary for any modern including measurement and feedback control strategies that are necessary for any
manufacturing process. modern manufacturing process.
The goal of this dissertation was to develop a microcarrier-based \gls{dms} T The goal of this dissertation was to develop a microcarrier-based \gls{dms} T
cell expansion system and determine biologically-meaningful \glspl{cqa} and cell expansion system and determine biologically-meaningful \glspl{cqa} and
\glspl{cpp} that could be used to optimize for highly-potent T cells. In \glspl{cpp} that could be used to optimize for highly-potent T cells. In
\cref{aim1}, we develop and characterized the \gls{dms} system, including \cref{aim1}, we develop and characterized the \gls{dms} system, including
quality control steps. We also demonstrate the feasiblity of expanding quality control steps. We also demonstrate the feasibility of expanding
high-quality T cells. In \cref{aim2a,aim2b}, we use \gls{doe} methodology to high-quality T cells. In \cref{aim2a,aim2b}, we use \gls{doe} methodology to
optimize the \gls{dms} platform, and develop a computational pipeline to optimize the \gls{dms} platform, and we develop a computational pipeline to
identify and model the effect of measurable \glspl{cqa}, and \glspl{cpp} on the identify and model the effects of measurable \glspl{cqa} and \glspl{cpp} on the
final product. In \cref{aim3}, we demonstrate the effectiveness of the \gls{dms} final product. In \cref{aim3}, we demonstrate the effectiveness of the \gls{dms}
platform \invivo{}. This thesis lays the groundwork for a novel T cell expansion platform \invivo{}. This thesis lays the groundwork for a novel T cell expansion
method which can be utilized at scale for a clinical trial and beyond. method which can be utilized at scale for clinical trials and beyond.
\clearpage \clearpage