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    Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent. 
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    • Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent.
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    • Centre for Molecular Oncology
    • Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent.
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    Re-designing Interleukin-12 to enhance its safety and potential as an anti-tumor immunotherapeutic agent.

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    Published version (2.249Mb)
    Volume
    8
    Pagination
    1395 - ?
    DOI
    10.1038/s41467-017-01385-8
    Journal
    Nat Commun
    Issue
    1
    Metadata
    Show full item record
    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.
    Authors
    Wang, P; Li, X; Wang, J; Gao, D; Li, Y; Li, H; Chu, Y; Zhang, Z; Liu, H; Jiang, G
    URI
    http://qmro.qmul.ac.uk/xmlui/handle/123456789/33983
    Collections
    • Centre for Molecular Oncology [256]
    Language
    eng
    Licence information
    Creative Commons Attribution License
    Copyright statements
    The Author(s) 2017
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