NDLI: Enhancement of Vaccinia Virus Based Oncolysis with Histone Deacetylase Inhibitors

Content Provider	PubMed Central
Author	Mactavish, Heather Diallo, Jean-simon Huang, Baocheng Stanford, Marianne Boeuf, Fabrice Le Silva, Naomi De Cox, Julie Simmons, John Graydon Guimond, Tanya Falls, Theresa Mccart, J. Andrea Atkins, Harry Breitbach, Caroline Kirn, David Thorne, Stephen Bell, John C.
Editor	Jin, Dong-yan
Abstract	Histone deacetylase inhibitors (HDI) dampen cellular innate immune response by decreasing interferon production and have been shown to increase the growth of vesicular stomatitis virus and HSV. As attenuated tumour-selective oncolytic vaccinia viruses (VV) are already undergoing clinical evaluation, the goal of this study is to determine whether HDI can also enhance the potency of these poxviruses in infection-resistant cancer cell lines. Multiple HDIs were tested and Trichostatin A (TSA) was found to potently enhance the spread and replication of a tumour selective vaccinia virus in several infection-resistant cancer cell lines. TSA significantly decreased the number of lung metastases in a syngeneic B16F10LacZ lung metastasis model yet did not increase the replication of vaccinia in normal tissues. The combination of TSA and VV increased survival of mice harbouring human HCT116 colon tumour xenografts as compared to mice treated with either agent alone. We conclude that TSA can selectively and effectively enhance the replication and spread of oncolytic vaccinia virus in cancer cells.
Related Links	http://dx.doi.org/10.1371/journal.pone.0014462
Starting Page	14462
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	12
Volume Number	5
Language	English
Publisher	Public Library of Science
Publisher Date	2010-12-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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