HBsAg-redirected T cells exhibit antiviral activity in HBV-infected human liver chimeric mice.
Cytotherapy
; 20(5): 697-705, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29631939
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Linfócitos T
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Quimera
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Vírus da Hepatite B
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Antígenos de Superfície da Hepatite B
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Fígado
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cytotherapy
Assunto da revista:
TERAPEUTICA
Ano de publicação:
2018
Tipo de documento:
Article