title: γδ T cell activation by bispecific antibodies.
abstract: Bispecific antibodies have been successfully introduced into clinical application. γδ T cells are of special interest for tumor immunotherapy, due to their recognition of pyrophosphates that are overproduced by many tumor cells resulting in HLA-nonrestricted tumor cell killing. Here we describe in detail a [(Her2)2 × Vγ9] tribody construct that targets human Vγ9 T cells to HER2-expressing tumor cells. The direct comparison with other selective Vγ9 T cell agonists including phosphoantigens and nitrogen-containing bisphosphonates revealed the superiority of the [(Her2)2 × Vγ9] tribody in triggering γδ T cell-mediated tumor cell killing with negligible induction of γδ T cell death. In contrast, phosphoantigens and bisphosphonates are potent inducers of γδ T cell proliferation but less efficient enhancers of γδ T cell-mediated tumor cell killing. Collectively, our data identify unique properties of a γδ T cell-targeting [(Her2)2 × Vγ9] tribody which make it an attractive candidate for clinical application in γδ T cell-based tumor immunotherapy.
authors.affiliation: Institute of Immunology, Christian-Albrechts-University, Kiel, Germany. Electronic address: Hans-Heinrich.Oberg@uksh.de.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University, Kiel, Germany. Electronic address: c.kellner@med2.uni-kiel.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Kellner
authors.affiliation: Institute of Immunology, Christian-Albrechts-University, Kiel, Germany. Electronic address: Daniel.Gonnermann@uksh.de.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonnermann
authors.affiliation: Division of Stem Cell Transplantation and Immunotherapy, Christian-Albrechts-University, Kiel, Germany. Electronic address: m.peipp@med2.uni-kiel.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Peipp
authors.affiliation: Institute of Immunology, Christian-Albrechts-University, Kiel, Germany. Electronic address: Christian.Peters@uksh.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Peters
authors.affiliation: Institute for Experimental Medicine, Christian-Albrechts-University, Kiel, Germany. Electronic address: mueerkoe@1med.uni-kiel.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Sebens
authors.affiliation: Institute of Immunology, Christian-Albrechts-University, Kiel, Germany. Electronic address: Dietrich.Kabelitz@uksh.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.affiliation: Institute of Immunology, Christian-Albrechts-University, Kiel, Germany. Electronic address: Daniela.Wesch@uksh.de.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
mesh_terms: D018033:Antibodies, Bispecific / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D011756:Diphosphates / Q000276:immunology; D004164:Diphosphonates / Q000276:immunology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D011756:Diphosphates; D004164:Diphosphonates; D018719:Erb-b2 Receptor Tyrosine Kinases; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521522:T-cell receptor Vgamma9, human; C508053:ERBB2 protein, human
keywords: Bispecific antibodies; Cytotoxicity; Gammadelta T lymphocytes; Human; Pancreatic ductal adenocarcinoma