Designer bacteria as intratumoural enzyme biofactories

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dc.contributor.authorLehouritis, Panos
dc.contributor.authorHogan, Glenn
dc.contributor.authorTangney, Mark
dc.contributor.funderIrish Cancer Societyen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderBreakthrough Cancer Research, Irelanden
dc.date.accessioned2017-10-05T10:32:58Z
dc.date.available2017-10-05T10:32:58Z
dc.date.issued2017-09-12
dc.date.updated2017-10-05T09:30:12Z
dc.description.abstractBacterial-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.en
dc.description.sponsorshipIrish Cancer Society (PCI12TAN);en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationLehouritis, P., Hogan, G. and Tangney, M. (2017) 'Designer bacteria as intratumoural enzyme biofactories', Advanced Drug Delivery Reviews, In Press. doi:10.1016/j.addr.2017.09.012en
dc.identifier.doi10.1016/j.addr.2017.09.012
dc.identifier.endpage16en
dc.identifier.issn0169-409X
dc.identifier.journaltitleAdvanced Drug Delivery Reviewsen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/4835
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Career Development Award/15/CDA/3630/IE/Edible Probiotics As Cancer Theranostics/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/612219/EU/Vaccines and Imaging Partnership/VIPen
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0169409X1730193X
dc.rights© 2017 Elsevier B.V. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectTumouren
dc.subjectDEPTen
dc.subjectProdrugen
dc.subjectCanceren
dc.subjectChemotherapyen
dc.subjectDrug designen
dc.subjectSynthetic biologyen
dc.subjectTargeteden
dc.subjectTranslational researchen
dc.subjectR&Den
dc.titleDesigner bacteria as intratumoural enzyme biofactoriesen
dc.typeArticle (peer-reviewed)en
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