(497e) Targeted Extracellular Vesicles to Deliver Chemotherapies to Treat Glioblastomas

Glioblastoma multiform is the most prevalent and aggressive primary malignant brain tumor, accounting for approximately 50 % of gliomas. The current standard cares such as surgery followed by radiotherapy and temozolomide (TMZ) only provides a median survival of 14.6 months. This study aimed to develop and evaluate a new targeted chemotherapy using the natural payload, verrucarin A (Ver-A), delivered with monoclonal antibody conjugated extracellular vesicles (mAb-EVs). Briefly, the high expression of epidermal growth factor receptor (EGFR) on glioblastoma was confirmed with immunohistochemistry staining of patient tissue microarray, Western blotting and flow cytometry using multiple cell lines. A large-scale biomanufacturing was developed to produce high-quality EVs to load the potent Ver-A and conjugated with anti-EGFR mAb. Confocal microscopy and In Vivo Imaging System analysis revealed that mAb-EVs could target glioblastoma tumor in xenograft mouse model, and specifically deliver Ver-A intracellularly both in vitro and in vivo. The cytotoxicity assays demonstrated the high anti-glioblastoma efficiency while tolerated study showed minimal toxicity in normal organs. Finally, in vivo anti-tumor efficacy studies using intracranial xenograft models demonstrated revealed EGFR mAb-EV-Ver-A effectively inhibited glioblastoma growth. The study suggested that mAb-EV-Ver-A is a promising targeted therapy to treat glioblastoma.