Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells

  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

  • Cancer Research

    Cancer Research 74 (5), 1349-1360, 2014-03-01

    American Association for Cancer Research (AACR)

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