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Dissertation
Optimization of T Cell Manufacturing in a Centrifugal Bioreactor Prototype and Transference of Related Concepts to the Undergraduate Classroom
Washington State University
Doctor of Philosophy (PhD), Washington State University
2023
DOI:
https://doi.org/10.7273/000005146
Abstract
Cancer remains a leading cause of death globally, and extensive evidence shows promising results with immunotherapy treatments, where the adaptive immune response is used to fight cancer without damaging healthy tissue. T cells are an immune cell that can be isolated from a patient's blood sample, grown to large numbers externally, and reintroduced to the patient. Adoption of this life-changing treatment is limited by the lack of methods for rapidly expanding T cells. To address this manufacturing bottleneck, a centrifugal bioreactor (CBR) was developed over the course of this dissertation that retains cells in a conical chamber by balancing centrifugal forces with a continuous feed of nutrient-filled medium, promoting optimal growth and preventing product loss. To study the efficacy of the CBR for cancer immunotherapy, proof-of-concept studies were performed with bovine cytotoxic T lymphocytes (CTLs) produced as an immune response to the parasite Theileria parva (T. parva), which induces uncontrolled proliferation of cells in African cattle like human blood cancers. Batch culture experiments defined a cell-specific kinetic growth model, used to determine manufacturing limits and predict ideal operating parameters in the CBR. Design recommendations are put forward to enhance commercialization potential of the CBR for cancer immunotherapy. Furthermore, aspects of the CBR design can be portrayed with microbeads suspended in solution to be used as a classroom-safe hands-on learning tool. Chemical engineers frequently contribute to the advancement of the medical field; however, such applications are often only covered in elective courses. To introduce medical applications into the undergraduate curriculum, a hands-on learning tool that portrays blood separation principles was implemented in a core chemical engineering class. Conceptual assessments, feedback surveys, and retention interviews were used to determine best practices for hands-on learning implementations. This dissertation encompasses optimization of T cell production in a CBR prototype for cancer immunotherapy with translation of design principles into a hands-on learning tool for undergraduate chemical engineering education, highlighting the impact of collaboration and interdisciplinary research.
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Details
- Title
- Optimization of T Cell Manufacturing in a Centrifugal Bioreactor Prototype and Transference of Related Concepts to the Undergraduate Classroom
- Creators
- Kitana Manivone Kaiphanliam
- Contributors
- Bernard J Vanwie (Advisor)William C Davis (Committee Member)Olusola O Adesope (Committee Member)David B Thiessen (Committee Member)Di Wu (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Chemical Engineering and Bioengineering, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 228
- Identifiers
- 99901019231201842
- Language
- English
- Resource Type
- Dissertation