| |  Online-Ressource |
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| Verfasst von: | Krämer, Christopher [VerfasserIn]  |
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| | Kilian, Michael [VerfasserIn] |
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| | Chih, Yu-Chan [VerfasserIn] |
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| | Kourtesakis, Alexandros [VerfasserIn] |
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| | Hoffmann, Dirk C. [VerfasserIn] |
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| | Boschert, Tamara [VerfasserIn] |
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| | Koopmann, Philipp [VerfasserIn] |
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| | Sanghvi, Khwab [VerfasserIn] |
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| | De Roia, Alice [VerfasserIn] |
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| | Jung, Stefanie [VerfasserIn] |
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| | Jähne, Kristine [VerfasserIn] |
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| | Day, Bryan [VerfasserIn] |
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| | Shultz, Lenny D. [VerfasserIn] |
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| | Ratliff, Miriam [VerfasserIn] |
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| | Harbottle, Richard [VerfasserIn] |
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| | Green, Edward W [VerfasserIn] |
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| | Will, Rainer [VerfasserIn] |
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| | Wick, Wolfgang [VerfasserIn] |
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| | Platten, Michael [VerfasserIn] |
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| | Bunse, Lukas [VerfasserIn] |
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| Titel: | NLGN4X TCR transgenic T cells to treat gliomas |
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| Verf.angabe: | Christoper Krämer, Michael Kilian, Yu-Chan Chih, Alexandros Kourtesakis, Dirk C Hoffmann, Tamara Boschert, Philipp Koopmann, Khwab Sanghvi, Alice De Roia, Stefanie Jung, Kristine Jähne, Bryan Day, Lenny D Shultz, Miriam Ratliff, Richard Harbottle, Edward W Green, Rainer Will, Wolfgang Wick, Michael Platten, and Lukas Bunse |
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| E-Jahr: | 2023 |
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| Jahr: | 16 September 2023 |
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| Umfang: | 14 S. |
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| Fussnoten: | Gesehen am 08.01.2024 |
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| Titel Quelle: | Enthalten in: Neuro-Oncology |
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| Ort Quelle: | Oxford : Oxford Univ. Press, 1999 |
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| Jahr Quelle: | 2023 |
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| Band/Heft Quelle: | (2023), Artikel-ID noad172, Seite 1-14 |
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| ISSN Quelle: | 1523-5866 |
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| Abstract: | Background. Neuroligin 4 X-linked (NLGN4X) harbors a human leukocyte antigen (HLA)-A*02-restricted tumorassociated antigen, overexpressed in human gliomas, that was found to induce specific cytotoxic T cell responses following multi-peptide vaccination in patients with newly diagnosed glioblastoma. - Methods. T cell receptor (TCR) discovery was performed using droplet-based single-cell TCR sequencing of NLGN4X-tetramer-sorted T cells postvaccination. The identified TCR was delivered to Jurkat T cells and primary human T cells (NLGN4X-TCR-T). Functional profiling of NLGN4X-TCR-T was performed by flow cytometry and cytotoxicity assays.Therapeutic efficacy of intracerebroventricular NLGN4X-TCR-T was assessed in NOD scid gamma (NSG) major histocompatibility complex (MHC) I/II knockout (KO) (NSG MHC I/II KO) mice bearing NLGN4Xexpressing experimental gliomas. - Results. An HLA-A*02-restricted vaccine-induced T cell receptor specifically binding NLGN4X131-139 was applied for preclinical therapeutic use. Reactivity, cytotoxicity, and polyfunctionality of this NLGN4X-specificTCR are demonstrated in various cellular models. Intracerebroventricular administration of NLGN4X-TCR-T prolongs survival and leads to an objective response rate of 44.4% in experimental glioma-bearing NSG MHC I/II KO mice compared to 0.0% in control groups. - Conclusion. NLGN4X-TCR-T demonstrate efficacy in a preclinical glioblastoma model. On a global scale, we provide the first evidence for the therapeutic retrieval of vaccine-induced human TCRs for the off-the-shelf treatment of glioblastoma patients.Keywords cell therapy | glioblastoma | T cell receptor | tumor antigen |
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| DOI: | doi:10.1093/neuonc/noad172 |
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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.
kostenfrei: Volltext: https://doi.org/10.1093/neuonc/noad172 |
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| | kostenfrei: Volltext: https://academic.oup.com/neuro-oncology/advance-article/doi/10.1093/neuonc/noad172/7275527 |
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| | DOI: https://doi.org/10.1093/neuonc/noad172 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| K10plus-PPN: | 1877432997 |
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| Verknüpfungen: | → Zeitschrift |
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NLGN4X TCR transgenic T cells to treat gliomas / Krämer, Christopher [VerfasserIn]; 16 September 2023 (Online-Ressource)
