From fb98f0699bbe9f21e1746cab77c376d3d8065ce5 Mon Sep 17 00:00:00 2001 From: ndwarshuis Date: Thu, 22 Jul 2021 13:48:51 -0400 Subject: [PATCH] ADD specific aims overview --- tex/thesis.tex | 49 ++++++++++++++++++++++++++++++++++++++++++++++--- 1 file changed, 46 insertions(+), 3 deletions(-) diff --git a/tex/thesis.tex b/tex/thesis.tex index 113bea9..dbccc2f 100644 --- a/tex/thesis.tex +++ b/tex/thesis.tex @@ -348,9 +348,52 @@ its effectiveness both \invivo{} and \invivo{}, and develop computational pipelines that could be used in a manufacturing environment. \section*{specific aims} -\subsection*{aim 1} -\subsection*{aim 2} -\subsection*{aim 3} + +The specific aims of this dissertation are outlined in +\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}