Change search
ReferencesLink to record
Permanent link

Direct link
An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors
Show others and affiliations
2013 (English)In: Mol Ther, Vol. 21, no 11, 2008-18 p.Article in journal (Refereed) Published
Abstract [en]

Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori infection. HP-NAP can mediate antitumor effects by recruiting neutrophils and inducing Th1-type differentiation in the tumor microenvironment. It therefore holds strong potential as a therapeutic gene. Here, we armed a replication-selective, infection-enhanced adenovirus with secretory HP-NAP, Ad5PTDf35-[Delta24-sNAP], and evaluated its therapeutic efficacy against neuroendocrine tumors. We observed that it could specifically infect and eradicate a wide range of tumor cells lines from different origin in vitro. Insertion of secretory HP-NAP did not affect the stability or replicative capacity of the virus and infected tumor cells could efficiently secrete HP-NAP. Intratumoral administration of the virus in nude mice xenografted with neuroendocrine tumors improved median survival. Evidence of biological HP-NAP activity was observed 24 hours after treatment with neutrophil infiltration in tumors and an increase of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and MIP2-alpha in the systemic circulation. Furthermore, evidence of Th1-type immune polarization was observed as a result of increase in IL-12/23 p40 cytokine concentrations 72 hours postvirus administration. Our observations suggest that HP-NAP can serve as a potent immunomodulator in promoting antitumor immune response in the tumor microenvironment and enhance the therapeutic effect of oncolytic adenovirus.

Place, publisher, year, edition, pages
2013. Vol. 21, no 11, 2008-18 p.
Keyword [en]
Adenoviridae/*genetics/metabolism, Animals, Bacterial Proteins/genetics/immunology/*therapeutic use, Cell Differentiation/drug effects, Cell Line, Tumor, Cytokines/metabolism, Female, Genetic Therapy, Genetic Vectors, Humans, Mice, Mice, Nude, Neuroendocrine Tumors/immunology/*therapy, Neutrophils/drug effects/metabolism, Oncolytic Virotherapy, Oncolytic Viruses/*genetics/metabolism, Recombination, Genetic, Tumor Microenvironment/drug effects/immunology, Virulence Factors/metabolism, Xenograft Model Antitumor Assays
National Category
Basic Medicine
URN: urn:nbn:se:umu:diva-110926ISBN: 1525-0024 (Electronic) 1525-0016 (Linking)OAI: diva2:865859

Ramachandran, Mohanraj Yu, Di Wanders, Alkwin Essand, Magnus Eriksson, Fredrik eng Research Support, Non-U.S. Gov't 2013/07/03 06:00 Mol Ther. 2013 Nov;21(11):2008-18. doi: 10.1038/mt.2013.153. Epub 2013 Jul 2.

Available from: 2015-10-29 Created: 2015-10-29 Last updated: 2015-10-29

Open Access in DiVA

No full text

Other links

Search in DiVA

By author/editor
Wanders, A.
Basic Medicine

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 22 hits
ReferencesLink to record
Permanent link

Direct link