ADD specific aims overview
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@ -348,9 +348,52 @@ its effectiveness both \invivo{} and \invivo{}, and develop computational
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pipelines that could be used in a manufacturing environment.
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pipelines that could be used in a manufacturing environment.
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\section*{specific aims}
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\section*{specific aims}
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\subsection*{aim 1}
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\subsection*{aim 2}
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The specific aims of this dissertation are outlined in
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\subsection*{aim 3}
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\cref{fig:graphical_overview}.
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\begin{figure*}[ht!]
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\begingroup
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\includegraphics[width=\textwidth]{example-image-a}
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\endgroup
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\caption[Project Overview]{High-level workflow.}
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\label{fig:graphical_overview}
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\end{figure*}
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\subsection*{aim 1: develop and optimize a novel T cell expansion process that
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mimics key components of the lymph nodes}
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% TODO this might be easier to break apart in separate aims
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In this first aim, we demonstrated the process for manufacturing \glspl{dms},
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including quality control steps that are necessary for translation of this
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platform into a scalable manufacturing setting. We also demonstrate that the
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\gls{dms} platform leads to higher overall expansion of T cells and higher
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overall fractions of potent memory and CD4+ subtypes desired for T cell
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therapies. Finally, we demonstrate \invitro{} that the \gls{dms} platform can be
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used to generate functional \gls{car} T cells targeted toward CD19.
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\subsection*{aim 2: develop methods to control and predict T cell quality}
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For this second aim, we investigated methods to identify and control \glspl{cqa}
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and glspl{cpp} for manufacturing T cells using the \gls{dms} platform. This was
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accomplished through two sub-aims:
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\begin{itemize}
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\item[A --] Develop computational methods to control and predict T cell
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expansion and quality
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\item[B --] Perturb \gls{dms} expansion to identify additional mechanistic
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controls for expansion and quality
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\end{itemize}
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\subsection*{aim 3: confirm potency of T cells from novel T cell expansion
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process using \invivo{} xenograft mouse model}
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In this final aim, we demonstrate the effectiveness of \gls{dms}-expanded T
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cells compared to state-of-the-art beads using \invivo{} mouse models for
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\gls{all}.
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\section*{outline}
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\section*{outline}
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