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An infection-enhanc...
An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors
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- Ramachandran, Mohanraj, 1988- (författare)
- Uppsala universitet,Klinisk immunologi
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- Yu, Di, 1985- (författare)
- Uppsala universitet,Klinisk immunologi,Magnus Essand
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- Wanders, Alkwin (författare)
- Uppsala universitet,Molekylär och morfologisk patologi
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- Essand, Magnus (författare)
- Uppsala universitet,Klinisk immunologi
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- Eriksson, Fredrik (författare)
- Uppsala universitet,Klinisk immunologi
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(creator_code:org_t)
- Nature Publishing Group, 2013
- 2013
- Engelska.
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Ingår i: Molecular Therapy. - : Nature Publishing Group. - 1525-0016 .- 1525-0024. ; 21:11, s. 2008-2018
- Relaterad länk:
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http://www.cell.com/...
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http://www.ncbi.nlm....
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- 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
- Molekylär medicin
- Klinisk virologi
- Medical Virology
- Klinisk immunologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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