Document Detail


Internalization of oncolytic reovirus by human dendritic cell carriers protects the virus from neutralization.
MedLine Citation:
PMID:  21389099     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Dendritic cells (DC) may be the most effective way of delivering oncolytic viruses to patients. Reovirus, a naturally occurring oncolytic virus, is currently undergoing early clinical trials; however, intravenous delivery of the virus is hampered by pre-existing antiviral immunity. Systemic delivery via cell carriage is a novel approach currently under investigation and initial studies have indicated its feasibility by using a variety of cell types and viruses. This study addressed the efficacy of human DC to transport virus in the presence of human neutralizing serum.
EXPERIMENTAL DESIGN: Following reovirus-loading, DC or T cells were cocultured with melanoma cells with or without neutralizing serum; the melanoma cells were then analyzed for cell death. Following reovirus loading, cells were examined by electron microscopy to identify mechanisms of delivery. The phagocytic function of reovirus-loaded DC was investigated by using labeled tumor cells and the ability of reovirus-loaded DC to prime T cells was also investigated.
RESULTS: In the presence of human neutralizing serum DC, but not T cells, were able to deliver reovirus for melanoma cell killing in vitro. Electron microscopy suggested that DC protected the virus by internalization, whereas with T cells it remained bound to the surface and hence accessible to neutralizing antibodies. Furthermore, DC loaded with reovirus were fully functional with regard to phagocytosis and priming of specific antitumor immune responses.
CONCLUSIONS: The delivery of reovirus via DC could be a promising new approach offering the possibility of combining systemic viral therapy for metastatic disease with induction of an antitumor immune response.
Authors:
Elizabeth J Ilett; Montserrat Bárcena; Fiona Errington-Mais; Stephen Griffin; Kevin J Harrington; Hardev S Pandha; Matthew Coffey; Peter J Selby; Ronald W A L Limpens; Mieke Mommaas; Rob C Hoeben; Richard G Vile; Alan A Melcher
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Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-09
Journal Detail:
Title:  Clinical cancer research : an official journal of the American Association for Cancer Research     Volume:  17     ISSN:  1078-0432     ISO Abbreviation:  Clin. Cancer Res.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-05-03     Completed Date:  2011-09-15     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  9502500     Medline TA:  Clin Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2767-76     Citation Subset:  IM    
Copyright Information:
©2011 AACR.
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MeSH Terms
Descriptor/Qualifier:
Antibodies, Neutralizing / adverse effects*
Cell Line, Tumor
Cytotoxicity, Immunologic / physiology
Dendritic Cells / immunology,  metabolism,  physiology,  virology*
Drug Carriers
Endocytosis / physiology
Humans
Melanoma / pathology,  therapy
Oncolytic Virotherapy* / methods
Oncolytic Viruses / metabolism*,  physiology
Reoviridae / metabolism,  physiology*
Skin Neoplasms / pathology,  therapy
T-Lymphocytes / immunology,  virology
Treatment Outcome
Viral Load / physiology
Virus Internalization*
Grant Support
ID/Acronym/Agency:
A5922//Cancer Research UK; CA RO1107082-02/CA/NCI NIH HHS; R01 CA107082/CA/NCI NIH HHS; R01 CA130878/CA/NCI NIH HHS; R01130878//PHS HHS; //Cancer Research UK
Chemical
Reg. No./Substance:
0/Antibodies, Neutralizing; 0/Drug Carriers
Comments/Corrections

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