Intratumoural production of TNF alpha by bacteria mediates cancer therapy

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dc.contributor.author Murphy, Carola T.
dc.contributor.author Rettedal, Elizabeth
dc.contributor.author Lehouritis, Panos
dc.contributor.author Devoy, Ciaran
dc.contributor.author Tangney, Mark
dc.date.accessioned 2017-09-26T11:39:20Z
dc.date.available 2017-09-26T11:39:20Z
dc.date.issued 2017
dc.identifier.citation Murphy, C., Rettedal, E., Lehouritis, P., Devoy, C. and Tangney, M. (2017) 'Intratumoural production of TNFα by bacteria mediates cancer therapy', PLoS ONE, 12(6), e0180034 (13pp). doi: 10.1371/journal.pone.0180034 en
dc.identifier.volume 12
dc.identifier.issued 6
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/4791
dc.identifier.doi 10.1371/journal.pone.0180034
dc.description.abstract Systemic administration of the highly potent anticancer therapeutic, tumour necrosis factor alpha (TNF alpha) induces high levels of toxicity and is responsible for serious side effects. Consequently, tumour targeting is required in order to confine this toxicity within the locality of the tumour. Bacteria have a natural capacity to grow within tumours and deliver therapeutic molecules in a controlled fashion. The non-pathogenic E. co/istrain MG1655 was investigated as a tumour targeting system in order to produce TNF alpha specifically within murine tumours. In vivo bioluminescence imaging studies and ex vivo immunofluorescence analysis demonstrated rapid targeting dynamics and prolonged survival, replication and spread of this bacterial platform within tumours. An engineered TNF alpha producing construct deployed in mouse models via either intra-tumoural (i.t.) or intravenous (i.v.) administration facilitated robust TNF alpha production, as evidenced by ELISA of tumour extracts. Tumour growth was impeded in three subcutaneous murine tumour models (CT26 colon, RENCA renal, and TRAMP prostate) as evidenced by tumour volume and survival analyses. A pattern of pro inflammatory cytokine induction was observed in tumours of treated mice vs. controls. Mice remained healthy throughout experiments. This study indicates the therapeutic efficacy and safety of TNF alpha expressing bacteria in vivo, highlighting the potential of non-pathogenic bacteria as a platform for restricting the activity of highly potent cancer agents to tumours. en
dc.description.sponsorship Irish Cancer Society (PCI12TAN) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.relation.uri http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180034
dc.rights © 2017, Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject Necrosis factor alpha en
dc.subject Gene therapy en
dc.subject Ionizing radiation en
dc.subject DNA delivery en
dc.subject Tumor growth en
dc.subject Salmonella en
dc.subject Transcription en
dc.subject Melanoma en
dc.subject Vector en
dc.subject System en
dc.title Intratumoural production of TNF alpha by bacteria mediates cancer therapy en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Mark Tangney, Cork Cancer Research Centre, University College Cork, Cork, Ireland. +353-21-490-3000 Email: m.tangney@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000404608300090
dc.contributor.funder Breakthrough Breast Cancer
dc.contributor.funder Seventh Framework Programme
dc.contributor.funder Irish Cancer Society
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLoS ONE en
dc.internal.IRISemailaddress m.tangney@ucc.ie en
dc.identifier.articleid e0180034
dc.relation.project info:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/612219/EU/Vaccines and Imaging Partnership/VIP


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© 2017, Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as © 2017, Murphy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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