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There is now a CONTENT FREEZE for Mercury while we switch to a new platform. It began on Friday, March 10 at 6pm and will end on Wednesday, March 15 at noon. No new content can be created during this time, but all material in the system as of the beginning of the freeze will be migrated to the new platform, including users and groups. Functionally the new site is identical to the old one. webteam@gatech.edu
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Nate Dwarshuis
PhD Thesis Defense Presentation
Date:2021-08-17
Time: 1:00 pm
Location / Meeting Link: https://bluejeans.com/286473768/1556
Committee Members:
Krishnendu Roy, PhD (Advisor)
Madhav Dhodapkar, MD
Melissa Kemp, PhD
Wilbur Lam, MD/PhD
Sakis Mantalaris, PhD
Title: Optimizing T Cell Manufacturing and Quality Using Functionalized Degradable Microscaffolds
Abstract: Adoptive cell therapies (ACT) using 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 anti-CD28 mAbs, usually mounted on magnetic beads. This method fails to recapitulate many key signals found in vivo and is also heavily licensed by a few companies, limiting its long-term usefulness to manufactures and clinicians. Furthermore, highly potent anti-tumor T cells are generally less-differentiated subtypes such as central memory T cells 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 dissertation was to develop a microcarrier-based DMS T cell expansion system and determine biologically-meaningful CQAs and critical process parameters (CPPs) that could be used to optimize for highly-potent T cells. We developed and characterized the DMS system, including quality control steps and also demonstrate the feasiblity of expanding high-quality T cells. Furthermore, we used design of experiments (DOE) methodology to optimize the DMS platform, and develop a computational pipeline to identify and model the effect of measurable CQAs, and CPPs on the final product. Finally, we demonstrated the effectiveness of the DMS platform in vivo. This work lays the groundwork for a novel T cell expansion method which can be utilized at scale for a clinical trial and beyond.
