Glioblastoma is a deadly brain cancer with discouraging standard of care. New methods like convection enhanced delivery and chimeric antigen receptor T cells (CAR-T) are promising treatments that can be translated to glioblastoma. In this study, CAR-T cell flow through a hydrogel was explored in the context of in-vitro convection enhanced delivery. A culture method to create large spheroids mimicking tumors from preexisting glioblastoma stem cell lines was fabricated, a convection enhanced delivery system for in-vitro testing was designed, and characterization of the CAR-T cells using the in-vitro system took place. The spheroid culture method was successfully optimized to produce spheroids large enough to act as a sufficient tumor in little time, the in-vitro set-up successfully administered treatment, and CAR-T cells were found to increase their velocities through a medium as their injection velocity increased. It was discovered that the density of the spheroid plays a crucial role in treatment delivery, often times driving how treatment will move through the spheroid. This system can be used in the future studies to test the killing potential of CAR-T cells to a tumor in-vitro. / Master of Science / Glioblastoma is a deadly brain cancer with current treatments that are discouraging at best. New methods must be utilized to aid in patient recovery. Chimeric antigen receptor T-Cells (CAR-T) are a promising treatment that can be used in glioblastoma. In this study, CAR-T cell behavior is defined in the context of in-vitro convection enhanced delivery. A large spheroid, or sphere of cells, mimicking a tumor was created, a convection enhanced delivery system set-up for in-vitro testing was designed, and characterization of CAR-T cell behavior using the in-vitro system took place. The spheroids were successfully cultured to act as a sufficient tumor, the in-vitro set-up successfully administered treatment, and CAR-T cells were found to increase their velocities in a gel as their injection velocity increases. It was discovered that the density of the spheroid plays a crucial role in treatment delivery, often times driving how treatment will move through the spheroid. This system can be used in the future studies to test the killing potential of CAR-T cells to a tumor in-vitro.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/110333 |
| Date | 25 May 2022 |
| Creators | Brocke, Conner Ethan |
| Contributors | Biological Systems Engineering, Senger, Ryan S., Munson, Jennifer M., Chen, Juhong |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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