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Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5

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Author(s): Sandra Lüttgau | Dorothée Deppe | Saskia Meyer | Regina Fertig | Hossein Panjideh | Martin Lipp | Oliver Schmetzer | Antonio Pezzutto | Frank Breitling | Gerhard Moldenhauer

Journal: Antibodies
ISSN 2073-4468

Volume: 2;
Issue: 2;
Start page: 338;
Date: 2013;
Original page

Keywords: bispecific antibody | lymphoma targeting | immunotherapy | CD19 | CD5

ABSTRACT
Using genetic engineering a humanized Fab fragment with specificity for CD19 was fused to a disulfide-stabilized single-chain antibody (dsFv) recognizing CD5. This format should show reduced immunogenicity and improved tissue penetration. The specificity of bsAb FabCD19xdsFvCD5 binding to target cells was verified by flow cytometry on B and T lymphoma cell lines. Binding affinities of both arms were compared with the bivalent parental antibodies against CD19 and CD5 by binding competition assay. Redirected lysis of B lymphoma cells by preactivated PBMC from healthy donors was demonstrated in a chromium-release assay. A clear dose-response relationship could be established in the range from 1 ng/mL to 10 mg/mL bsAb. To evaluate the in vivo efficacy of bsAb FabCD19xdsFvCD5, NOD/SCID mice were intravenously injected with luciferase transfected Raji lymphoma cells together with pre-activated PBMC. Mice received five injections of therapeutic bsAb or control antibodies. While in the control groups all mice died within 40 to 50 days, 40% of bsAb treated animals survived longer than 60 days.
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