57 lines
2.1 KiB
TeX
57 lines
2.1 KiB
TeX
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\documentclass{article}
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\usepackage[top=1in,left=1in,right=1in,bottom=1in]{geometry}
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\usepackage{setspace}
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\pagestyle{empty}
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\begin{document}
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\begin{center}
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\LARGE{\textbf{Optimizing T Cell Manufacturing and Quality Using
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Functionalized Degradable Microscaffolds}}
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\Large
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\bigskip
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Nathan J. Dwarshuis
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\bigskip
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165 pages
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\bigskip
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Directed by Krishnendu Roy
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\end{center}
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\large
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\doublespacing{}
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Adoptive cell therapy using chimeric antigen receptor (CAR) T cells have shown
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promise in treating cancer, but manufacturing large numbers of high quality
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cells remains challenging. Currently approved T cell expansion technologies
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involve anti-CD3 and anti-CD28 antibodies, usually mounted on magnetic beads.
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This method fails to recapitulate many key signals found \textit{in vivo} and is
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also heavily licensed by a few companies, limiting its long-term usefulness to
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manufactures and clinicians. Furthermore, highly potent, anti-tumor T cells are
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generally less-differentiated subtypes such as central memory and stem memory T
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cells. Despite this understanding, little has been done to optimize T cell
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expansion for generating these subtypes, including measurement and feedback
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control strategies that are necessary for any modern manufacturing process.
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The goal of this dissertation was to develop a microcarrier-based degradable
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microscaffold (DMS) T cell expansion system and determine
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biologically-meaningful critical quality attitudes and critical process
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parameters that could be used to optimize for highly-potent T cells. We
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developed and characterized the DMS system, including quality control steps. We
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also demonstrated the feasibility of expanding high-quality T cells. We used
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Design of Experiments methodology to optimize the DMS platform, and we developed
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a computational pipeline to identify and model the effects of measurable
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critical quality attributes and critical process parameters on the final
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product. Finally, we demonstrated the effectiveness of the DMS platform
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\textit{in vivo}. This thesis lays the groundwork for a novel T cell expansion
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method which can be utilized at scale for clinical trials and beyond.
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\end{document}
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