Investigating the Efficacy of CAR T-Cells Expressing TQM-13 in Targeting Glioblastoma

Open Access
- Author:
- Jiang, Hali A
- Area of Honors:
- Biomedical Engineering
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Cheng Dong, Thesis Supervisor
Dr. Justin Lee Brown, Thesis Honors Advisor - Keywords:
- CAR T
Immunotherapy
Glioblastoma
T-lymphocytes
TQM-13 - Abstract:
- Chimeric antigen receptor (CAR) modified T-cell therapy has proven to be an attractive immunotherapy that involves the genetic modification of T-lymphocytes to target specific antigens expressed by cancer cells. Recent research has shown promising results for CAR T-cells expressing Targeted Quadruple Mutant-13 (TQM-13), a mutant version of interleukin-13 (IL-13), in targeting and attacking glioblastoma multiforme (GBM). CAR T immunotherapy is able to utilize the inherent ability of T-lymphocyte cells to migrate across the blood-brain barrier (BBB), a specialized, highly selective, semipermeable membrane formed by neurovascular endothelial cells that restrict the substances that enter and exit the central nervous system. Additionally, the CAR modification leads to specialized targeting of a specific antigen displayed by the tumor of interest. Once attached and bound to the target, the CAR T-cell becomes activated leading to T-cell proliferation, secretion of apoptosis-inducing proteins, and subsequent destruction of the tumor cells. The present study examines the ability of CAR T-cells expressing TQM-13 to target GBM. The results indicate that CAR modification did not impede the cells’ natural ability to form intercellular gaps nor their ability to extravasate through an endothelial layer, both crucial steps in crossing the BBB. Additionally, it was found that CAR modification significantly increased both the total number of adhesions observed as well as the length of time the CAR T-cells adhered to GBM cells under flow conditions. These results imply that a TQM-13 directed CAR design has the potential to be a powerful therapeutic tool in the treatment of GBM.