title: A Recombinant Bispecific CD20×CD95 Antibody With Superior Activity Against Normal and Malignant B-cells.
abstract: Monoclonal antibodies directed to the B-cell-specific CD20-antigen are successfully used for the treatment of lymphomas and autoimmune diseases. Here, we compare the anti-B-cell activity of three different antibodies directed to CD20: (i) a chimeric, monospecific antibody, (ii) an Fc-optimized variant thereof, and (iii) a bispecific CD20×CD95-antibody in a newly developed recombinant format, termed Fabsc. The bispecific antibody specifically triggers the CD95 death receptor on malignant, as well as activated, normal B-cells. We found that the capability of this antibody to suppress the growth of malignant B-cells in vitro and in vivo and to specifically deplete normal, activated B-cells from peripheral blood mononuclear cell (PBMC) cultures was superior to that of the Fc-optimized monospecific antibody. This antibody in turn was more effective than its nonoptimized variant. Moreover, the bispecific antibody was the only reagent capable of significantly suppressing antibody production in vitro. Our findings imply that the bispecific CD20×CD95-antibody might become a new, prototypical reagent for the treatment of B-cell-mediated autoimmune disease.
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Nalivaiko
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany; Current address: Synimmune GmbH, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Hofmann
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany.
authors.forename: Karina
authors.initials: K
authors.lastname: Kober
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany; Current address: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Teichweyde
authors.affiliation: Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Krammer
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany; Current address: Synimmune GmbH, Tübingen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Grosse-Hovest
authors.affiliation: Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: Gundram.Jung@uni-tuebingen.de.
authors.forename: Gundram
authors.initials: G
authors.lastname: Jung
mesh_terms: D000818:Animals; D018033:Antibodies, Bispecific / Q000008:administration & dosage* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D016393:Lymphoma, B-Cell / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D019014:fas Receptor / Q000276:immunology*
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D019014:fas Receptor