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Mol Ther. 2016 Feb;24(2):298-305. doi: 10.1038/mt.2015.209. Epub 2015 Nov 19.

A Recombinant Bispecific CD20×CD95 Antibody With Superior Activity Against Normal and Malignant B-cells.

Author information

  • 1Department of Immunology, Eberhard Karls Universität Tübingen, Tübingen, Germany.
  • 2Current address: Synimmune GmbH, Tübingen, Germany.
  • 3Current address: Institute for Transfusion Medicine, University Hospital Essen, Essen, Germany.
  • 4Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 5German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.

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.

PMID:
26581163
PMCID:
PMC4817817
DOI:
10.1038/mt.2015.209
[PubMed - indexed for MEDLINE]
Free PMC Article
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