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Antibodies 2013, 2(2), 338-352; doi:10.3390/antib2020338
Article

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

1, 1, 1, 1, 2, 2, 3, 3,4, 5 and 1,*
1 Department of Translational Immunology, German Cancer Research Center and National Center for Tumor Diseases, 69120 Heidelberg, Germany 2 Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center of Molecular Medicine, 13125 Berlin, Germany 3 Molecular Immunotherapy, Max-Delbrück Center of Molecular Medicine, 13125 Berlin, Germany 4 Department of Hematology, Oncology and Tumor Immunology, Charité Universitätsmedizin, 13353 Berlin, Germany 5 Department Peptide Arrays and Antibody Libraries, Karlsruhe Institute of Technology (KIT), 76344 Eggenstein-Leopoldshafen, Germany
* Author to whom correspondence should be addressed.
Received: 26 March 2013 / Revised: 22 April 2013 / Accepted: 22 April 2013 / Published: 14 May 2013
(This article belongs to the Special Issue Bispecific Antibodies for Dual Targeting Strategies)
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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.
Keywords: bispecific antibody; lymphoma targeting; immunotherapy; CD19; CD5 bispecific antibody; lymphoma targeting; immunotherapy; CD19; CD5
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Lüttgau, S.; Deppe, D.; Meyer, S.; Fertig, R.; Panjideh, H.; Lipp, M.; Schmetzer, O.; Pezzutto, A.; Breitling, F.; Moldenhauer, G. Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5. Antibodies 2013, 2, 338-352.

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