ADD specific aims overview

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Nathan Dwarshuis 2021-07-22 13:48:51 -04:00
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@ -348,9 +348,52 @@ its effectiveness both \invivo{} and \invivo{}, and develop computational
pipelines that could be used in a manufacturing environment. pipelines that could be used in a manufacturing environment.
\section*{specific aims} \section*{specific aims}
\subsection*{aim 1}
\subsection*{aim 2} The specific aims of this dissertation are outlined in
\subsection*{aim 3} \cref{fig:graphical_overview}.
\begin{figure*}[ht!]
\begingroup
\includegraphics[width=\textwidth]{example-image-a}
\endgroup
\caption[Project Overview]{High-level workflow.}
\label{fig:graphical_overview}
\end{figure*}
\subsection*{aim 1: develop and optimize a novel T cell expansion process that
mimics key components of the lymph nodes}
% TODO this might be easier to break apart in separate aims
In this first aim, we demonstrated the process for manufacturing \glspl{dms},
including quality control steps that are necessary for translation of this
platform into a scalable manufacturing setting. We also demonstrate that the
\gls{dms} platform leads to higher overall expansion of T cells and higher
overall fractions of potent memory and CD4+ subtypes desired for T cell
therapies. Finally, we demonstrate \invitro{} that the \gls{dms} platform can be
used to generate functional \gls{car} T cells targeted toward CD19.
\subsection*{aim 2: develop methods to control and predict T cell quality}
For this second aim, we investigated methods to identify and control \glspl{cqa}
and glspl{cpp} for manufacturing T cells using the \gls{dms} platform. This was
accomplished through two sub-aims:
\begin{itemize}
\item[A --] Develop computational methods to control and predict T cell
expansion and quality
\item[B --] Perturb \gls{dms} expansion to identify additional mechanistic
controls for expansion and quality
\end{itemize}
\subsection*{aim 3: confirm potency of T cells from novel T cell expansion
process using \invivo{} xenograft mouse model}
In this final aim, we demonstrate the effectiveness of \gls{dms}-expanded T
cells compared to state-of-the-art beads using \invivo{} mouse models for
\gls{all}.
\section*{outline} \section*{outline}