| |  Online-Ressource |
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| Verfasst von: | Schönfeld, Kurt [VerfasserIn]  |
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| | Holtgreve-Grez, Heidi [VerfasserIn] |
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| | Jauch, Anna [VerfasserIn] |
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| | Schmidt, Manfred [VerfasserIn] |
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| Titel: | Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor |
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| Verf.angabe: | Kurt Schönfeld, Christiane Sahm, Congcong Zhang, Sonja Naundorf, Christian Brendel, Marcus Odendahl, Paulina Nowakowska, Halvard Bönig, Ulrike Köhl, Stephan Kloess, Sylvia Köhler, Heidi Holtgreve-Grez, Anna Jauch, Manfred Schmidt, Ralf Schubert, Klaus Kühlcke, Erhard Seifried, Hans G. Klingemann, Michael A. Rieger, Torsten Tonn, Manuel Grez, Winfried S. Wels |
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| Jahr: | 2015 |
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| Jahr des Originals: | 2014 |
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| Umfang: | 9 S. |
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| Fussnoten: | Published online: 9 December 2014 ; Gesehen am 28.04.2017 |
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| Titel Quelle: | Enthalten in: Molecular therapy |
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| Ort Quelle: | Amsterdam : Elsevier, 2000 |
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| Jahr Quelle: | 2015 |
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| Band/Heft Quelle: | 23(2015), 2, Seite 330-338 |
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| ISSN Quelle: | 1525-0024 |
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| Abstract: | Natural killer (NK) cells are an important effector cell type for adoptive cancer immunotherapy. Similar to T cells, NK cells can be modified to express chimeric antigen receptors (CARs) to enhance antitumor activity, but experience with CAR-engineered NK cells and their clinical development is still limited. Here, we redirected continuously expanding and clinically usable established human NK-92 cells to the tumor-associated ErbB2 (HER2) antigen. Following GMP-compliant procedures, we generated a stable clonal cell line expressing a humanized CAR based on ErbB2-specific antibody FRP5 harboring CD28 and CD3ζ signaling domains (CAR 5.28.z). These NK-92/5.28.z cells efficiently lysed ErbB2-expressing tumor cells in vitro and exhibited serial target cell killing. Specific recognition of tumor cells and antitumor activity were retained in vivo, resulting in selective enrichment of NK-92/5.28.z cells in orthotopic breast carcinoma xenografts, and reduction of pulmonary metastasis in a renal cell carcinoma model, respectively. γ-irradiation as a potential safety measure for clinical application prevented NK cell replication, while antitumor activity was preserved. Our data demonstrate that it is feasible to engineer CAR-expressing NK cells as a clonal, molecularly and functionally well-defined and continuously expandable cell therapeutic agent, and suggest NK-92/5.28.z cells as a promising candidate for use in adoptive cancer immunotherapy. |
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| DOI: | doi:10.1038/mt.2014.219 |
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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: http://dx.doi.org/10.1038/mt.2014.219 |
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| | DOI: https://doi.org/10.1038/mt.2014.219 |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Animals |
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| | Breast Neoplasms |
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| | Cell Line, Transformed |
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| | Cell Line, Tumor |
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| | Clonal Evolution |
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| | Cytotoxicity, Immunologic |
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| | Disease Models, Animal |
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| | Epitopes, T-Lymphocyte |
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| | Female |
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| | Gene Expression |
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| | Genetic Vectors |
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| | Humans |
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| | Immunophenotyping |
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| | Immunotherapy |
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| | Killer Cells, Natural |
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| | Lentivirus |
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| | Lymphocyte Culture Test, Mixed |
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| | Neoplasms |
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| | Phenotype |
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| K10plus-PPN: | 1557310130 |
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| Verknüpfungen: | → Zeitschrift |
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Selective inhibition of tumor growth by clonal NK cells expressing an ErbB2/HER2-specific chimeric antigen receptor / Schönfeld, Kurt [VerfasserIn]; 2015 (Online-Ressource)
