Abstract 6696: Exosome delivered combinatorial therapeutic approaches for advanced brain tumors

Abstract Glioblastoma (GBM) is an aggressive form of brain cancer that affects over 12, 000 people each year in the United States. Current treatments such as surgery, chemotherapy, and radiation have limitations and can often fail to achieve full tumor remission, as the five-year survival rate for this disease is around 7%. Recent research has revealed miRNA (miR), small non-coding RNAs that regulate gene expression, as contributors to the suppression and progression of various cancers, including GBM. Exosomes, tiny vesicles released by cells, show great promise as a cancer therapeutic. Our research focuses on using exosomes enriched with microRNA (miR) to address miR dysregulation in as a delivery system for glioblastoma treatment, as these vessels can cross the blood-brain barrier to deliver the treatment. Our goal is to examine the effectiveness of stem cell-derived exosomes carrying miR-124 and miR-7 as a new approach for treating glioblastoma, as this cancer is known for having downregulation of such microRNAs. Adult human stem cells (SC) are modified with target miR plasmids and then grown in an exosome-depleted medium. The exosomes that carry the miR are then separated, purified, measured, and examined. These exosomes are used in all subsequent research. The effects of exosomes on established and patient derived primary GBM cells are studied using a combination of cell viability tests and microscopy. To understand the molecular mechanisms that underlie the effect of miR modulation on cell proliferation and cell death pathways, a time course immunoblot analysis is carried out. To assess the effects of miR modulation in vivo, orthotopic animal models of GBM will be used. Our research has shown that stem cell-derived exosomes can be an effective delivery system, asthey can evade the immune system and target specific cells. We have successfully transferred microRNA cargo to our target tumor cells using exosomes. By modulating miR, we have been able to halt tumor progression in vitro by targeting multiple pathways involved in GBM growth and progression. Although we are still awaiting the results of our ongoing animal studies, our preliminary data suggests that using stem cell-derived exosomes loaded with miR-124 and miR-7 is a promising approach for treating GBM. Citation Format: Monique Kanitz Ruschel, Isaiah Davis, Karthik Gourishetti, Christian Jacobsen, Deepak Bhere. Exosome delivered combinatorial therapeutic approaches for advanced brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6696.