DDIS-10. ENGINEERED EXOSOMES FOR GLIOMA THERAPY

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2018-11, Vol.20 (suppl_6), p.vi71-vi71
• Main Authors: Hossain, Anwar, Hasan, Irtiza, Adachi, Satoshi, Gumin, Joy, Kerrigan, Brittany, Lang, Frederick
• Format: Article
• Language: English
• Subjects: Abstracts
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noy148.289

Abstract Glioblastoma (GBM) is the most common among all malignant brain tumors, with 17,000 diagnoses every year in the United States. Despite receiving surgery, radiotherapy, and chemotherapy, the median survival of GBM patients is only 14.6 months, and less than 10% of GBM patients survive more than 5 years. There is an urgent need for the development of more effective therapies. To this end, we have developed a novel method to deliver therapeutic antiglioma genes by exploiting exosomes derived from engineered HEK293 cells that can package plasmid DNA (pDNA), messenger RNA (mRNA) or microRNA (miRNA). These exosomes are modified using ligand display technologies to allow delivery of cargo to cell types of choice. For proof of concept we used the glioma cell line U87 containing a “floxed” dsR cassette upstream of a green fluorescent protein (eGFP) transgene; in the absence of the cre these cells express red fluorescent protein. Transfer of either cre expressing pDNA or mRNA using engineered exosomes induced cre recombinse-mediated excision of the floxed tdTomato cassette, and subsequent expression of eGFP in vitro as well as in in vivo glioma models. In addition to using engineered exosomes to deliver cre, we also successfully delivered both luciferase and cytosine deaminase-uracil phosphoribosyl transferase. This model provides a unique functional readout demonstrating that engineered exosomes can be used to deliver any functional genetic cargoes to the cell of choice. This technology allows the delivery of pDNA/mRNA/miRNA to treat GBMs, and has powerful implications for a broad range of biotherapeutics: cancer therapy, cancer vaccines or immunotherapeutics, and DNA editing (CRISPR/Cas9).