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