dc.contributor.author | Wang, P | en_US |
dc.contributor.author | Li, X | en_US |
dc.contributor.author | Wang, J | en_US |
dc.contributor.author | Gao, D | en_US |
dc.contributor.author | Li, Y | en_US |
dc.contributor.author | Li, H | en_US |
dc.contributor.author | Chu, Y | en_US |
dc.contributor.author | Zhang, Z | en_US |
dc.contributor.author | Liu, H | en_US |
dc.contributor.author | Jiang, G | en_US |
dc.contributor.author | Cheng, Z | en_US |
dc.contributor.author | Wang, S | en_US |
dc.contributor.author | Dong, J | en_US |
dc.contributor.author | Feng, B | en_US |
dc.contributor.author | Chard, LS | en_US |
dc.contributor.author | Lemoine, NR | en_US |
dc.contributor.author | Wang, Y | en_US |
dc.date.accessioned | 2018-02-28T13:10:24Z | |
dc.date.available | 2017-09-14 | en_US |
dc.date.issued | 2017-11-09 | en_US |
dc.date.submitted | 2018-02-22T12:31:50.476Z | |
dc.identifier.other | 10.1038/s41467-017-01385-8 | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/33983 | |
dc.description.abstract | Interleukin-12 (IL-12) has emerged as one of the most potent agents for anti-tumor immunotherapy. However, potentially lethal toxicity associated with systemic administration of IL-12 precludes its clinical application. Here we redesign the molecule in such a way that its anti-tumor efficacy is not compromised, but toxic effects are eliminated. Deletion of the N-terminal signal peptide of IL-12 can effect such a change by preventing IL-12 secretion from cells. We use a newly designed tumor-targeted oncolytic adenovirus (Ad-TD) to deliver non-secreting (ns) IL-12 to tumor cells and examine the therapeutic and toxic effects in Syrian hamster models of pancreatic cancer (PaCa). Strikingly, intraperitoneal delivery of Ad-TD-nsIL-12 significantly enhanced survival of animals with orthotopic PaCa and cured peritoneally disseminated PaCa with no toxic side effects, in contrast to the treatment with Ad-TD expressing unmodified IL-12. These findings offer renewed hope for development of IL-12-based treatments for cancer. | en_US |
dc.description.sponsorship | This project was supported by the National Natural Science Foundation of China
(81272525 and 81201792), Ministry of Science and Technology of China
(2013DFG32080) and The MRC (MR/M015696/1). | en_US |
dc.format.extent | 1395 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | Creative Commons Attribution License | |
dc.subject | Adenoviridae | en_US |
dc.subject | Animals | en_US |
dc.subject | Antineoplastic Agents | en_US |
dc.subject | CD8-Positive T-Lymphocytes | en_US |
dc.subject | Cell Line, Tumor | en_US |
dc.subject | Cricetinae | en_US |
dc.subject | Disease Models, Animal | en_US |
dc.subject | Female | en_US |
dc.subject | Gene Transfer Techniques | en_US |
dc.subject | Humans | en_US |
dc.subject | Immunotherapy | en_US |
dc.subject | Interleukin-12 | en_US |
dc.subject | Oncolytic Virotherapy | en_US |
dc.subject | Oncolytic Viruses | en_US |
dc.subject | Pancreatic Neoplasms | en_US |
dc.subject | Xenograft Model Antitumor Assays | en_US |
dc.title | Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent. | en_US |
dc.type | Article | |
dc.rights.holder | The Author(s) 2017 | |
dc.identifier.doi | 10.1038/s41467-017-01385-8 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29123084 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | No embargo | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 8 | en_US |
dcterms.dateAccepted | 2017-09-14 | en_US |
qmul.funder | Development of an effective therapeutic regimen for treatment of advanced pancreatic cancer using a novel immunotherapeutic agent::Medical Research Council | en_US |