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Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo

Cancer Gene Therapy volume 24, pages 38–44 (2017)Cite this article

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Abstract

Extracellular vesicles (EVs) are considered as important mediators of intercellular communication, which carry a diverse repertoire of genetic information between cells. This feature of EVs can be used and improved to advance their therapeutic potential. We have previously shown that genetically engineered EVs carrying the suicide gene mRNA and protein—cytosine deaminase (CD) fused to uracil phosphoribosyltransferase (UPRT)—inhibited schwannoma tumor growth in vivo. To further examine whether this approach can be applied to other cancer types, we established a subcutaneous xenograft glioblastoma tumor model in mice, as glioblastoma represents the most common primary brain tumor, which is highly aggressive compared with the original schwannoma tumor model. U87-MG glioblastoma cells were implanted into the flanks of nude SCID mice, and the animals were intratumorally injected with the EVs isolated from the cells expressing EGFP or CD-UPRT. After the intraperitoneal administration of the prodrug 5-fluorocytosine, the tumor growth was assessed by regular caliper measurements. Our data revealed that the treatment with the CD-UPRT-enriched EVs significantly reduced the tumor growth in mice. Taken together, our findings suggest that EVs uploaded with therapeutic CD-UPRT mRNA/protein may be a useful tool for glioblastoma treatment.

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Acknowledgements

This work was supported, in part, by Melodie Privatstiftung (NS), EU-FP7-PEOPLE-2011-CIG (OS) and the Children's Cancer Research Institute St Anna Cancer Research Fund-0017 (OS).

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Author notes

  1. E P Erkan

    Present address: 3Current address: Pharmaplus Ilac ve Saglik Urunleri, Dokuz Eylul University Health Technopark (DEPARK), Izmir, Turkey.,

  2. E P Erkan and D Senfter: Co-first authors.

  3. N Saydam and O Saydam: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics and Adolescent Medicine, Molecular Neuro-Oncology Research Unit, Medical University of Vienna, Vienna, Austria

    E P Erkan, D Senfter, S Madlener, G Jungwirth, N Saydam & O Saydam

  2. Institute of Neurology, Medical University of Vienna, Vienna, Austria

    T Ströbel

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  1. E P Erkan
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Correspondence to N Saydam or O Saydam.

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Supplementary Information accompanies the paper on Cancer Gene Therapy website

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Erkan, E., Senfter, D., Madlener, S. et al. Extracellular vesicle-mediated suicide mRNA/protein delivery inhibits glioblastoma tumor growth in vivo. Cancer Gene Ther 24, 38–44 (2017). https://doi.org/10.1038/cgt.2016.78

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