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    
Abstract/OtherAbstract:
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.
Authors:
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
Related Documents :
23823317 - Intracellular nad+-depletion enhances bortezomib-induced anti-myeloma activity.
23565187 - Liposomal lipopolysaccharide initiates trif-dependent signaling pathway independent of ...
9548797 - Inorganic and methylated arsenic compounds induce cell death in murine macrophages via ...
23880957 - Inflammatory mediators alter interleukin-17 receptor, interleukin-12 and -23 expression...
17058227 - In vivo immune modulatory activity of hepatic stellate cells in mice.
12411407 - Cyclosporine a regulate oxidative stress-induced apoptosis in cardiomyocytes: mechanism...
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    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Autoimmunity / drug effects
Cell Line, Tumor
Female
Histone Deacetylase Inhibitors / therapeutic use*
Immunotherapy / methods*
Melanoma / drug therapy,  therapy
Mice
Mice, Inbred C57BL
Neoplasms / drug therapy,  therapy*
Grant Support
ID/Acronym/Agency:
MOP-67066//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Histone Deacetylase Inhibitors
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Therapeutic effects of microRNA-582-5p and -3p on the inhibition of bladder cancer progression.
Next Document:  Hyaluronan enhances bone marrow cell therapy for myocardial repair after infarction.