Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells
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- Hans-Heinrich Oberg
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Matthias Peipp
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Christian Kellner
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Susanne Sebens
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Sarah Krause
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Domantas Petrick
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Sabine Adam-Klages
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Christoph Röcken
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Thomas Becker
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Ilka Vogel
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Dietrich Weisner
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Sandra Freitag-Wolf
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Martin Gramatzki
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Dieter Kabelitz
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
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- Daniela Wesch
- Authors' Affiliations: 1Institute of Immunology; 2Division of Stem Cell Transplantation and Immunotherapy; 3Institute for Experimental Medicine; 4Institute of Pathology; 5Clinic of General and Thoracic Surgery; 6Institute for Medical Informatics and Statistic, Christian-Albrechts-University Kiel; 7Municipal Hospital, Department of Surgery; and 8Clinic of Gynaecology and Obstetrics, Kiel, Germany
抄録
<jats:title>Abstract</jats:title><jats:p>The ability of human γδ T cells from healthy donors to kill pancreatic ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice requires the addition of γδ T-cell–stimulating antigens. In this study, we demonstrate that γδ T cells isolated from patients with PDAC tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. We determined the absolute numbers of γδ T-cell subsets in patient whole blood and applied a real-time cell analyzer to measure their cytotoxic effector function over prolonged time periods. Because phosphorylated antigens did not optimally enhance γδ T-cell cytotoxicity, we designed bispecific antibodies that bind CD3 or Vγ9 on γδ T cells and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies enhanced γδ T-cell cytotoxicity with the Her2/Vγ9 antibody also selectively enhancing release of granzyme B and perforin. Supporting these observations, adoptive transfer of γδ T cells with the Her2/Vγ9 antibody reduced growth of pancreatic tumors grafted into SCID-Beige immunocompromised mice. Taken together, our results show how bispecific antibodies that selectively recruit γδ T cells to tumor antigens expressed by cancer cells illustrate the tractable use of endogenous γδ T cells for immunotherapy. Cancer Res; 74(5); 1349–60. ©2014 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 74 (5), 1349-1360, 2014-03-01
American Association for Cancer Research (AACR)
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360011145755001856
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- ISSN
- 15387445
- 00085472
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- データソース種別
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- Crossref