The HDAC inhibitor zabadinostat is a systemic regulator of adaptive immunity.
Commun Biol
; 6(1): 102, 2023 01 26.
Article
in English
| MEDLINE | ID: covidwho-2212038
ABSTRACT
Protein acetylation plays a key role in regulating cellular processes and is subject to aberrant control in diverse pathologies. Although histone deacetylase (HDAC) inhibitors are approved drugs for certain cancers, it is not known whether they can be deployed in other therapeutic contexts. We have explored the clinical HDAC inhibitor, zabadinostat/CXD101, and found that it is a stand-alone regulator of the adaptive immune response. Zabadinostat treatment increased expression of MHC class I and II genes in a variety of cells, including dendritic cells (DCs) and healthy tissue. Remarkably, zabadinostat enhanced the activity of DCs, and CD4 and CD8 T lymphocytes. Using an antigenic peptide presented to the immune system by MHC class I, zabadinostat caused an increase in antigen-specific CD8 T lymphocytes. Further, mice immunised with covid19 spike protein and treated with zabadinostat exhibit enhanced covid19 neutralising antibodies and an increased level of T lymphocytes. The enhanced humoral response reflected increased activity of T follicular helper (Tfh) cells and germinal centre (GC) B cells. Our results argue strongly that zabadinostat has potential to augment diverse therapeutic agents that act through the immune system.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunity, Humoral
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Commun Biol
Year:
2023
Document Type:
Article
Affiliation country:
S42003-023-04485-y
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