Abstract
Background
Chronic hepatitis B virus (HBV) infection remains incurable. Although HBsAg-specific
chimeric antigen receptor (HBsAg-CAR) T cells have been generated, they have not been
tested in animal models with authentic HBV infection.
Methods
We generated a novel CAR targeting HBsAg and evaluated its ability to recognize HBV+
cell lines and HBsAg particles in vitro. In vivo, we tested whether human HBsAg-CAR T cells would have efficacy against HBV-infected
hepatocytes in human liver chimeric mice.
Results
HBsAg-CAR T cells recognized HBV-positive cell lines and HBsAg particles in vitro as judged by cytokine production. However, HBsAg-CAR T cells did not kill HBV-positive
cell lines in cytotoxicity assays. Adoptive transfer of HBsAg-CAR T cells into HBV-infected
humanized mice resulted in accumulation within the liver and a significant decrease
in plasma HBsAg and HBV-DNA levels compared with control mice. Notably, the fraction
of HBV core–positive hepatocytes among total human hepatocytes was greatly reduced
after HBsAg-CAR T cell treatment, pointing to noncytopathic viral clearance. In agreement,
changes in surrogate human plasma albumin levels were not significantly different
between treatment and control groups.
Conclusions
HBsAg-CAR T cells have anti-HBV activity in an authentic preclinical HBV infection
model. Our results warrant further preclinical exploration of HBsAg-CAR T cells as
immunotherapy for HBV.
Key Words
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Article info
Publication history
Published online: April 06, 2018
Accepted:
February 4,
2018
Received:
September 28,
2017
Identification
Copyright
© 2018 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
