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...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , |
|---|---|
| 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 
|
| 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 |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1671643135 | ||
| 003 | DE-627 | ||
| 005 | 20220816211932.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 190820s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1172/JCI120228 |2 doi | |
| 035 | |a (DE-627)1671643135 | ||
| 035 | |a (DE-599)KXP1671643135 | ||
| 035 | |a (OCoLC)1341238211 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Wisskirchen, Karin |e VerfasserIn |0 (DE-588)1193092779 |0 (DE-627)1671643933 |4 aut | |
| 245 | 1 | 0 | |a T cell receptor grafting allows virological control of hepatitis B virus infection |c 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 |
| 264 | 1 | |c June 10, 2019 | |
| 300 | |a 14 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 20.08.2019 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a adoptive transfer | |
| 650 | 4 | |a cancer regression | |
| 650 | 4 | |a cd8(+) | |
| 650 | 4 | |a chimeric antigen receptor | |
| 650 | 4 | |a expression | |
| 650 | 4 | |a hepatocytes | |
| 650 | 4 | |a humanized mice | |
| 650 | 4 | |a immunity | |
| 650 | 4 | |a replication | |
| 650 | 4 | |a viral clearance | |
| 700 | 1 | |a Kah, Janine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Malo, Antje |e VerfasserIn |4 aut | |
| 700 | 1 | |a Asen, Theresa |e VerfasserIn |4 aut | |
| 700 | 1 | |a Volz, Tassilo |e VerfasserIn |4 aut | |
| 700 | 1 | |a Allweiss, Lena |e VerfasserIn |4 aut | |
| 700 | 1 | |a Wettengel, Jochen M. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Luetgehetmann, Marc |e VerfasserIn |4 aut | |
| 700 | 1 | |a Urban, Stephan |e VerfasserIn |0 (DE-588)1060263599 |0 (DE-627)79935399X |0 (DE-576)174162049 |4 aut | |
| 700 | 1 | |a Bauer, Tanja |e VerfasserIn |4 aut | |
| 700 | 1 | |a Dandri-Petersen, Maura |e VerfasserIn |0 (DE-588)1027352030 |0 (DE-627)72898573X |0 (DE-576)37292977X |4 aut | |
| 700 | 1 | |a Protzer-Knolle, Ulrike |d 1962- |e VerfasserIn |0 (DE-588)112551920 |0 (DE-627)558726712 |0 (DE-576)289735092 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The journal of clinical investigation |d Ann Arbor, Mich. : ASCJ, 1924 |g 129(2019), 7, Seite 2932-2945 |h Online-Ressource |w (DE-627)316004677 |w (DE-600)2018375-6 |w (DE-576)094950423 |x 1558-8238 |7 nnas |a T cell receptor grafting allows virological control of hepatitis B virus infection |
| 773 | 1 | 8 | |g volume:129 |g year:2019 |g number:7 |g pages:2932-2945 |g extent:14 |a T cell receptor grafting allows virological control of hepatitis B virus infection |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1172/JCI120228 |x Resolving-System |x Verlag |3 Volltext |
| 856 | 4 | 0 | |u https://www.jci.org/articles/view/120228 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20190820 | ||
| 993 | |a Article | ||
| 994 | |a 2019 | ||
| 998 | |g 112551920 |a Protzer-Knolle, Ulrike |m 112551920:Protzer-Knolle, Ulrike |p 12 |y j | ||
| 998 | |g 1060263599 |a Urban, Stephan |m 1060263599:Urban, Stephan |d 910000 |d 911700 |e 910000PU1060263599 |e 911700PU1060263599 |k 0/910000/ |k 1/910000/911700/ |p 9 | ||
| 999 | |a KXP-PPN1671643135 |e 3507669919 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"media":"Online-Ressource","bibl":"article-journal"},"language":["eng"],"physDesc":[{"extent":"14 S."}],"title":[{"title_sort":"T cell receptor grafting allows virological control of hepatitis B virus infection","title":"T cell receptor grafting allows virological control of hepatitis B virus infection"}],"person":[{"display":"Wisskirchen, Karin","family":"Wisskirchen","role":"aut","given":"Karin"},{"role":"aut","given":"Janine","family":"Kah","display":"Kah, Janine"},{"display":"Malo, Antje","given":"Antje","role":"aut","family":"Malo"},{"display":"Asen, Theresa","role":"aut","given":"Theresa","family":"Asen"},{"family":"Volz","role":"aut","given":"Tassilo","display":"Volz, Tassilo"},{"display":"Allweiss, Lena","family":"Allweiss","given":"Lena","role":"aut"},{"display":"Wettengel, Jochen M.","family":"Wettengel","given":"Jochen M.","role":"aut"},{"given":"Marc","role":"aut","family":"Luetgehetmann","display":"Luetgehetmann, Marc"},{"display":"Urban, Stephan","family":"Urban","role":"aut","given":"Stephan"},{"display":"Bauer, Tanja","family":"Bauer","role":"aut","given":"Tanja"},{"display":"Dandri-Petersen, Maura","given":"Maura","role":"aut","family":"Dandri-Petersen"},{"display":"Protzer-Knolle, Ulrike","family":"Protzer-Knolle","role":"aut","given":"Ulrike"}],"recId":"1671643135","name":{"displayForm":["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"]},"origin":[{"dateIssuedKey":"2019","dateIssuedDisp":"June 10, 2019"}],"id":{"eki":["1671643135"],"doi":["10.1172/JCI120228"]},"note":["Gesehen am 20.08.2019"],"relHost":[{"title":[{"title_sort":"journal of clinical investigation","subtitle":"JCI ; the publication of the American Society for Clinical Investigation","title":"The journal of clinical investigation"}],"language":["eng"],"physDesc":[{"extent":"Online-Ressource"}],"corporate":[{"role":"isb","display":"American Society for Clinical Investigation"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"origin":[{"publisher":"ASCJ","dateIssuedKey":"1924","dateIssuedDisp":"1924-","publisherPlace":"Ann Arbor, Mich."}],"id":{"eki":["316004677"],"zdb":["2018375-6"],"issn":["1558-8238"]},"disp":"T cell receptor grafting allows virological control of hepatitis B virus infectionThe journal of clinical investigation","recId":"316004677","pubHistory":["1.1924/25 -"],"note":["Gesehen am 25.01.2022","Fortsetzung der Druck-Ausgabe"],"titleAlt":[{"title":"JCI"}],"part":{"text":"129(2019), 7, Seite 2932-2945","extent":"14","pages":"2932-2945","volume":"129","issue":"7","year":"2019"}}]} | ||
| SRT | |a WISSKIRCHETCELLRECEP1020 | ||