Poster #077, City of Hope
Evaluating the Use of CAR-T Cell Chemokine Secretion in Activating the Endogenous Immune System in DIPG
Mentors: Nour Amwas, MS, PI: Leo Wang, MD, PhD
Diffuse Intrinsic Pontine Glioma (DIPG) is a highly aggressive and deadly form of brain cancer in children. Chimeric Antigen Receptor (CAR) T cells are engineered to eliminate tumor cells by using receptors to recognize tumor-specific ligands. A major hurdle to CAR T response is the tumor-immune microenvironment of DIPG, which has few T and B cell infiltrates. This leads to CAR T exhaustion, as these cells rejuvenate CAR T cells. We hypothesized that engaging the endogenous immune system via chemokine-secreting CAR-Ts would promote a robust antitumor immune response by recruiting T and B Cells. 3 DNA constructs coding for chemokines were created, all with a backbone for the CAR: one for CCL13, attracting B cells, and for CCL21α and CCL19, recruiting T cells. We predict that this recruitment will lead to an increase in tumor necrosis. This will provide a potential method to increase the impact of immunotherapy on DIPG