Document Detail

HDAC inhibition suppresses primary immune responses, enhances secondary immune responses, and abrogates autoimmunity during tumor immunotherapy.
MedLine Citation:
PMID:  23295947     Owner:  NLM     Status:  MEDLINE    
Histone deacetylase inhibitors (HDACi) can modulate innate antiviral responses and render tumors more susceptible to oncolytic viruses (OVs); however, their effects on adaptive immunity in this context are largely unknown. Our present study reveals an unexpected property of the HDACi MS-275 that enhances viral vector-induced lymphopenia leading to selective depletion of bystander lymphocytes and regulatory T cells while allowing expansion of antigen-specific secondary responses. Coadministration of vaccine plus drug during the boosting phase focuses the immune response on the tumor by suppressing the primary immune response against the vaccine vector and enhancing the secondary response against the tumor antigen. Furthermore, improvement of T cell functionality was evident suggesting that MS-275 can orchestrate a complex array of effects that synergize immunotherapy and viral oncolysis. Surprisingly, while MS-275 dramatically enhanced efficacy, it suppressed autoimmune pathology, profoundly improving the therapeutic index.
Byram W Bridle; Lan Chen; Chantal G Lemay; Jean-Simon Diallo; Jonathan Pol; Andrew Nguyen; Alfredo Capretta; Rongqiao He; Jonathan L Bramson; John C Bell; Brian D Lichty; Yonghong Wan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-08
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  21     ISSN:  1525-0024     ISO Abbreviation:  Mol. Ther.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-01     Completed Date:  2013-11-01     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  United States    
Other Details:
Languages:  eng     Pagination:  887-94     Citation Subset:  IM    
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MeSH Terms
Autoimmunity / drug effects
Cell Line, Tumor
Histone Deacetylase Inhibitors / therapeutic use*
Immunotherapy / methods*
Melanoma / drug therapy,  therapy
Mice, Inbred C57BL
Neoplasms / drug therapy,  therapy*
Grant Support
MOP-67066//Canadian Institutes of Health Research
Reg. No./Substance:
0/Histone Deacetylase Inhibitors

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