Buchumschlag

T cell receptor grafting allows virological control of hepatitis B virus infection

T cell therapy is a promising means to treat chronic hepatitis B virus (HBV) infection and HBV-associated hepatocellular carcinoma. T cells engineered to express an HBV-specific T cell receptor (TCR) may cure an HBV infection upon adoptive transfer. We investigated the therapeutic potential and safe...

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Hauptverfasser: Wisskirchen, Karin (VerfasserIn) , Kah, Janine (VerfasserIn) , Malo, Antje (VerfasserIn) , Asen, Theresa (VerfasserIn) , Volz, Tassilo (VerfasserIn) , Allweiss, Lena (VerfasserIn) , Wettengel, Jochen M. (VerfasserIn) , Luetgehetmann, Marc (VerfasserIn) , Urban, Stephan (VerfasserIn) , Bauer, Tanja (VerfasserIn) , Dandri-Petersen, Maura (VerfasserIn) , Protzer-Knolle, Ulrike (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: June 10, 2019
In: The journal of clinical investigation
Year: 2019, Jahrgang: 129, Heft: 7, Pages: 2932-2945
ISSN:1558-8238
DOI:10.1172/JCI120228
Online-Zugang:Resolving-System, Volltext: http://dx.doi.org/10.1172/JCI120228
Verlag, Volltext: https://www.jci.org/articles/view/120228
Volltext
Verfasserangaben:Karin Wisskirchen, Janine Kah, Antje Malo, Theresa Asen, Tassilo Volz, Lena Allweiss, Jochen M. Wettengel, Marc Luetgehetmann, Stephan Urban, Tanja Bauer, Maura Dandri, and Ulrike Protzer
Beschreibung
Zusammenfassung:T cell therapy is a promising means to treat chronic hepatitis B virus (HBV) infection and HBV-associated hepatocellular carcinoma. T cells engineered to express an HBV-specific T cell receptor (TCR) may cure an HBV infection upon adoptive transfer. We investigated the therapeutic potential and safety of T cells stably expressing high-affinity HBV envelope- or core-specific TCRs recognizing European and Asian HLA-A2 subtypes. Both CD8(+) and CD4(+) T cells from healthy donors and patients with chronic hepatitis B became polyfunctional effector cells when grafted with HBV-specific TCRs and eliminated HBV from infected HepG2-NTCP cell cultures. A single transfer of TCR-grafted T cells into HBV-infected, humanized mice controlled HBV infection, and virological markers declined by 4 to 5 log or below the detection limit. Engineered T cells specifically cleared infected hepatocytes without damaging noninfected cells when, as in a typical clinical setting, only a minority of hepatocytes were infected. Cell death was compensated by hepatocyte proliferation, and alanine amino transferase levels peaking between days 5 and 7 normalized again thereafter. Cotreatment with the entry inhibitor myrcludex B ensured long-term control of HBV infection. Thus, T cells stably transduced with highly functional TCRs have the potential to mediate clearance of HBV-infected cells, causing limited liver injury.
Beschreibung:Gesehen am 20.08.2019
Beschreibung:Online Resource
ISSN:1558-8238
DOI:10.1172/JCI120228

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