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| Verfasst von: | Wisskirchen, Karin [VerfasserIn]  |
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| | Kah, Janine [VerfasserIn] |
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| | Malo, Antje [VerfasserIn] |
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| | Asen, Theresa [VerfasserIn] |
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| | Volz, Tassilo [VerfasserIn] |
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| | Allweiss, Lena [VerfasserIn] |
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| | Wettengel, Jochen M. [VerfasserIn] |
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| | Luetgehetmann, Marc [VerfasserIn] |
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| | Urban, Stephan [VerfasserIn] |
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| | Bauer, Tanja [VerfasserIn] |
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| | Dandri-Petersen, Maura [VerfasserIn] |
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| | Protzer-Knolle, Ulrike [VerfasserIn] |
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| Titel: | T cell receptor grafting allows virological control of hepatitis B virus infection |
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| Verf.angabe: | 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 |
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| E-Jahr: | 2019 |
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| Jahr: | June 10, 2019 |
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| Umfang: | 14 S. |
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| Fussnoten: | Gesehen am 20.08.2019 |
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| Titel Quelle: | Enthalten in: The journal of clinical investigation |
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| Ort Quelle: | Ann Arbor, Mich. : ASCJ, 1924 |
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| Jahr Quelle: | 2019 |
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| Band/Heft Quelle: | 129(2019), 7, Seite 2932-2945 |
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| ISSN Quelle: | 1558-8238 |
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| Abstract: | 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. |
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| DOI: | doi:10.1172/JCI120228 |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext ; Verlag: http://dx.doi.org/10.1172/JCI120228 |
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| | Volltext: https://www.jci.org/articles/view/120228 |
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| | DOI: https://doi.org/10.1172/JCI120228 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | adoptive transfer |
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| | cancer regression |
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| | cd8(+) |
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| | chimeric antigen receptor |
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| | expression |
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| | hepatocytes |
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| | humanized mice |
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| | immunity |
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| | replication |
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| | viral clearance |
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| K10plus-PPN: | 1671643135 |
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| Verknüpfungen: | → Zeitschrift |
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T cell receptor grafting allows virological control of hepatitis B virus infection / Wisskirchen, Karin [VerfasserIn]; June 10, 2019 (Online-Ressource)
