Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity.

Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Research Abstract Details 

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Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Abstract Text:

Anthony T Power,Jiahu Wang,Theresa J Falls,Jennifer M Paterson,Kelley A Parato,Brian D Lichty,David F Stojdl,Peter A J Forsyth,Harry Atkins,John C Bell,Anthony T Power,Jiahu Wang,Theresa J Falls,Jennifer M Paterson,Kelley A Parato,Brian D Lichty,David F Stojdl,Peter A J Forsyth,Harry Atkins,John C Bell,

Oncolytic viruses capable of tumor-selective replication and cytolysis have shown early promise as cancer therapeutics. However, the host immune system remains a significant obstacle to effective systemic administration of virus in a clinical setting. Here, we demonstrate the severe negative impact of the adaptive immune response on the systemic delivery of oncolytic vesicular stomatitis virus (VSV) in an immune-competent murine tumor model, an effect mediated primarily by the neutralization of injected virions by circulating antibodies. We show that this obstacle can be overcome by administering virus within carrier cells that conceal viral antigen during delivery. Infected cells were delivered to tumor beds and released virus to infect malignant cells while sparing normal tissues. Repeated administration of VSV in carrier cells to animals bearing metastatic tumors greatly improved therapeutic efficacy when compared with naked virion injection. Whole-body molecular imaging revealed that carrier cells derived from solid tumors accumulate primarily in the lungs following intravenous injection, whereas leukemic carriers disseminate extensively throughout the body. Furthermore, xenogeneic cells were equally effective at delivering virus as syngeneic cells. These findings emphasize the importance of establishing cell-based delivery platforms in order to maximize the efficacy of oncolytic therapeutics.Molecular Therapy (2007) 15, 123-130. doi:10.1038/sj.mt.6300039.

Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Publishing Authors By Initials

AT Power,J Wang,TJ Falls,JM Paterson,KA Parato,BD Lichty,DF Stojdl,PA Forsyth,H Atkins,JC Bell,AT Power,J Wang,TJ Falls,JM Paterson,KA Parato,BD Lichty,DF Stojdl,PA Forsyth,H Atkins,JC Bell,

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Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 123-30

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 13

MONTH: Jan

YEAR: 2007

Carrier Cell-based Delivery of an Oncolytic Virus Circumvents Antiviral Immunity. Information

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LANGUAGE: eng

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AFFILIATION: 1Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa Health Research Institute, Centre for Cancer Therapeutics, Ottawa, Ontario, Canada.

Country: United States

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MEDLINETA: Mol Ther

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