Presentation Time: 2:20-2:40
Home University: UNC-Chapel Hill
Research Mentor: Justin Milner, Microbiology and Immunology
Research Title: Enhancing the efficacy of chimeric antigen receptor T cells in pancreatic cancer
Antigen presentation machinery is often downregulated on malignant cells, limiting recognition and killing by CD8 T cells. However, tumor cells express tumor-specific surface molecules, such as B7-H3 or mesothelin, that can be detected by chimeric antigen receptors (CAR) engineered on T cells, and thus induce specific killing against the corresponding tumor cells. The objective of this project is to develop systems for manipulating CAR-T cell activity in preclinical mouse models. To do so, we first evaluated an elegant and well-established CAR-T cell system for pancreatic cancer wherein murine pancreatic cancer cells (KPC cells) stably express B7-H3. My project involved setting up an in vitro assay to test the killing efficacy of B7-H3 CAR-T cell in this model to establish a foundation for testing other novel CAR-T cell strategies. Experimentally, activated mouse T cells were infected by retroviruses that encode a murine adapted B7-H3 CAR. Next, transduced B7-H3 CAR- T cells were co-cultured with KPC B7-H3 tumor cells. Finally, the cells were analyzed via flow cytometry to determine CAR-T cell killing efficacy. While the results are pending, we expect B7-H3 CAR-T cells to demonstrate effective and antigen-specific killing of KPC B7-H3 tumor cells. Future studies will investigate the efficacy of new CAR-T systems and begin targeting critical regulators of T cell function to boost CAR-T cell efficacy.