Designer bacteria as intratumoural enzyme biofactories
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Accepted version
Date
2017-09-12
Authors
Lehouritis, Panos
Hogan, Glenn
Tangney, Mark
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Published Version
Abstract
Bacterial-directed enzyme prodrug therapy (BDEPT) is an emerging form of treatment for cancer. It is a biphasic variant of gene therapy in which a bacterium, armed with an enzyme that can convert an inert prodrug into a cytotoxic compound, induces tumour cell death following tumour-specific prodrug activation. BDEPT combines the innate ability of bacteria to selectively proliferate in tumours, with the capacity of prodrugs to undergo contained, compartmentalised conversion into active metabolites in vivo. Although BDEPT has undergone clinical testing, it has received limited clinical exposure, and has yet to achieve regulatory approval. In this article, we review BDEPT from the system designer's perspective, and provide detailed commentary on how the designer should strategize its development de novo. We report on contemporary advancements in this field which aim to enhance BDEPT in terms of safety and efficacy. Finally, we discuss clinical and regulatory barriers facing BDEPT, and propose promising approaches through which these hurdles may best be tackled.
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Keywords
Tumour , DEPT , Prodrug , Cancer , Chemotherapy , Drug design , Synthetic biology , Targeted , Translational research , R&D
Citation
Lehouritis, P., Hogan, G. and Tangney, M. (2017) 'Designer bacteria as intratumoural enzyme biofactories', Advanced Drug Delivery Reviews, In Press. doi:10.1016/j.addr.2017.09.012