A new immunotherapy can combat the hepatitis B virus, researchers have reported.
Scientists from UCL, UK, used immune cells isolated directly from patient liver and tumour tissue, to show that targeting acyl-CoA:cholesterol acyltransferase (ACAT) was highly effective at boosting immune responses.
Writing in the latest edition of Nature Communications, their findings show that blocking the activity of ACAT with ACAT inhibitors boosts the specific immune cells that can fight both the virus and associated cancerous tumours.
Slowing down ACAT also impeded HBV’s own replication, which meant it also acted as a direct antiviral.
In this study, Professor Mala Maini, of UCL Division of Infection & Immunity, UK, and colleagues used human liver disease tissue samples in vitro, which showed ACAT inhibitors boosted human antiviral T cells capable of eliminating the virus.
The immune-boosting effect was found to be particularly impressive in T cells found in the HBV-infected liver and within liver cancer as it overcame restraints on immune cell function and enabled the T cells to target the virus and cancerous cells.
Professor Jane McKeating at the University of Oxford and her team went on to show that ACAT inhibitors could also block the HBV life cycle in a way that other antivirals cannot, which means these drugs provide a unique combination of antiviral and immunotherapeutic effects.
First author Dr Nathalie Schmidt, of UCL Division of Infection & Immunity, said: “We have found a highly effective novel target for the treatment of chronic hepatitis B virus infection and liver cancer.
“Modulating cholesterol metabolism with ACAT inhibitors has the unique features of directly targeting the virus and tumours while at the same time boosting the T cells that fight them. This enables us to tackle the disease from multiple directions at the same time.”
The research was carried out by UCL and was supported by the University of Oxford, the Royal Free London NHS Trust, and Leiden University Medical Centre, the Netherlands. Grant funding came from the Wellcome Trust and Cancer Research UK.
Schmidt NM, Wing PAC, Diniz MO et al. Targeting human Acyl-CoA: cholesterol acyltransferase as a dual viral and T-cell metabolic checkpoint. Nature Communications 14 May 2021; doi: 10.1038/s41467-021-22967-7
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