Date of Award

10-2023

Document Type

Thesis

Degree Name

Master of Science in Biology

Department

Biology

First Reader/Committee Chair

Nicole Bournias Vardiabasis

Abstract

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs through electroporation. We have characterized the initial designs but have not yet generated a construct which definitively activates in the presence of C3aR positive D54-MG cells. An orthotopic xenograft model of D54-MG cells expressing luciferase in NOD-SCID gamma mice was characterized and dose optimized for minimum cell transplant to induce moribund signs at 3-4 weeks post transplantation. These combined results provide a solid foundation for the future in vitro and in vivo experiments supporting the rapid development of novel CAR T cell therapies against glioblastoma.

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