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Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors

MacTavish, H and Diallo, JS and Huang, B and Stanford, M and Le Boeuf, F and De Silva, N and Cox, J and Simmons, JG and Guimond, T and Falls, T and McCart, AJ and Atkins, H and Breitbach, C and Kirn, D and Thorne, S and Bell, JC (2010) Enhancement of vaccinia virus based oncolysis with histone deacetylase inhibitors. PLoS ONE, 5 (12).

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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. © 2010 MacTavish et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
MacTavish, H
Diallo, JS
Huang, B
Stanford, M
Le Boeuf, F
De Silva, N
Cox, J
Simmons, JG
Guimond, T
Falls, T
McCart, AJ
Atkins, H
Breitbach, C
Kirn, D
Thorne, Ssht38@pitt.eduSHT38
Bell, JC
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 1 December 2010
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 5
Number: 12
DOI or Unique Handle: 10.1371/journal.pone.0014462
Schools and Programs: School of Medicine > Immunology
School of Medicine > Surgery
Refereed: Yes
MeSH Headings: Animals; Cell Line, Tumor; Cell Survival; Histone Deacetylase Inhibitors--pharmacology; Humans; Hydroxamic Acids--pharmacology; Immune System; Interferons--metabolism; Melanoma, Experimental; Mice; Neoplasm Transplantation; Neoplasms--metabolism; Neoplasms--virology; Oncolytic Virotherapy--methods; Oncolytic Viruses--metabolism; Vaccinia virus--metabolism
Other ID: NLM PMC3012680
PubMed Central ID: PMC3012680
PubMed ID: 21283510
Date Deposited: 25 Aug 2012 16:39
Last Modified: 02 Feb 2019 16:58


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