ADD abstract

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Nathan Dwarshuis 2021-07-09 13:13:57 -04:00
parent 7aed0412ca
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\usepackage[capitalize]{cleveref}
\usepackage[version=4]{mhchem}
\usepackage{pgfgantt}
\usepackage{setspace}
\doublespacing
\titleformat{\section}[block]{\bfseries\large}{}{0pt}{\uppercase}
\titleformat{\subsection}[block]{\bfseries\large}{}{0pt}{\titlecap}
@ -33,10 +36,18 @@
\renewcommand{\glossarysection}[2][]{} % remove glossary title
\makeglossaries
\newacronym{act}{ACT}{adoptive cell therapies}
\newacronym{car}{CAR}{chimeric antigen receptor}
\newacronym[longplural={monoclonal antibodies}]{mab}{mAb}{monoclonal antibody}
\newacronym{ecm}{ECM}{extracellular matrix}
\newacronym{cqa}{CQA}{critical quality attribute}
\newacronym{cpp}{CPP}{critical process parameter}
\newacronym{dms}{DMS}{degradable microscaffold}
\newacronym{doe}{DOE}{design of experiments}
\begin{document}
\begin{titlepage}
\begin{singlespace}
\begin{center}
\huge\textbf{Optimizing T Cell Manufacturing and Quality Using
@ -98,6 +109,7 @@
Dr. Sakis Mantalaris \\
Wallace H. Coulter Department of Biomedical Engineering, Georgia
Institute of Technology and Emory University }
\end{singlespace}
\end{titlepage}
\onecolumn \pagenumbering{roman}
@ -116,7 +128,32 @@ Thank you to Lex Fridman and Devin Townsend for being awesome and inspirational.
\section*{abstract}
Insert abstract here.
\Gls{act} using \gls{car} T cells have shown promise in treating cancer, but
manufacturing large numbers of high quality cells remains challenging. Currently
approved T cell expansion technologies involve anti-CD3 and CD28 \glspl{mab},
usually mounted on magnetic beads. This method fails to recapitulate many key
signals found \textit{in vivo} and is also heavily licensed by a few companies,
limiting its long-term usefulness to manufactures and clinicians. Furthermore,
we understand that highly potent T cells are generally less-differentiated
subtypes such as central memory and stem memory T cells. Despite this
understanding, little has been done to optimize T cell expansion for generating
these subtypes, including measurement and feedback control strategies that are
necessary for any modern manufacturing process.
The goal of this thesis was to develop a microcarrier-based \gls{dms} T cell
expansion system as well as determine biologically-meaningful \glspl{cqa} and
\glspl{cpp} that could be used to optimize for highly-potent T cells. In Aim 1,
we develop and characterized the \gls{dms} system, including quality control
steps. We also demonstrate the feasiblity of expanding highly-potent memory and
CD4+ T cells, and showing compatibility with existing \gls{car} transduction
methods. In aim 2, we use \gls{doe} methodology to optimize the \gls{dms}
platform, and develop a computational pipeline to identify and model the effect
of measurable \glspl{cqa} and \glspl{cpp} on the final product. In aim 3, we
demonstrate the effectiveness of the \gls{dms} platform \textit{in vivo}. This
thesis lays the groundwork for a novel T cell expansion method which can be used
in a clinical setting, and also provides a path toward optimizing for product
quality in an industrial setting.
\clearpage