Abstract 3103: Intraparenchymal delivery of chemokines and immunomodulators to eliminate pediatric brain tumor cells

Abstract

Abstract Pediatric brain tumors are among the leading causes of cancer-related death in children. These malignancies tend to occur in locations of the brain where surgery and radiation can permanently impair a patient’s quality of life. Migratory cells from high grade brain tumors can invade nearby, inaccessible areas of the brain where they may grow unchecked and ultimately lead to patient death. This project seeks to tailor the microenvironment around the tumor cavity to promote the recruitment and elimination of remnant brain tumor cells by microglia and macrophages found in the brain. Our data suggests gradients of classical immune cell chemokines, like CCL2, are also potent chemotactic signals for a variety of patient-derived brain tumor types. Monoclonal antibody blockade of CD47, a cell-surface “don’t eat me” ligand often over-expressed on tumor cells, is effective at promoting the elimination of tumor cells in close-proximity to murine macrophages in vitro. We engineered user-programable hydrogel depots capable of month-long molecule release and implanted them into tumor-bearing mouse brains. Hydrogels incorporated with CCL2 and CD47mAb demonstrated statistically significant co-recruitment of tumor and immune cells and evidence of macrophage-mediated tumor cell death compared to PBS-incorporated gels. These results suggest proper stimulation of immune cells within the brain could be an effective means to eliminate pediatric brain tumor cells without causing structural damage to vital nervous tissues. Our data may be the first steps towards clinical trials for children with incompletely resected brain tumors. Citation Format: Eric S. Nealy, Cole A. DeForest, James Olson. Intraparenchymal delivery of chemokines and immunomodulators to eliminate pediatric brain tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3103.