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The HDAC inhibitor zabadinostat is a systemic regulator of adaptive immunity.
Liu, Geng; Barczak, Wojciech; Lee, Lian Ni; Shrestha, Amit; Provine, Nicholas M; Albayrak, Gulsah; Zhu, Hong; Hutchings, Claire; Klenerman, Paul; La Thangue, Nicholas B.
  • Liu G; Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
  • Barczak W; Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
  • Lee LN; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK.
  • Shrestha A; Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
  • Provine NM; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
  • Albayrak G; Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
  • Zhu H; Laboratory of Cancer Biology, Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, UK.
  • Hutchings C; Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, 610041, Chengdu, China.
  • Klenerman P; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK.
  • La Thangue NB; Peter Medawar Building for Pathogen Research, University of Oxford, Oxford, OX1 3SY, UK.
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.
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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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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