Next Article in Journal / Special Issue
The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM) Complexes
Previous Article in Journal
Characterization of a Phospho-Specific Antibody to the Fcε Receptor γ Chain, Reveals Differences in the Regulation of Syk and Akt Phosphorylation
Previous Article in Special Issue
Dual Targeting of Tumor Cells with Bispecific Single-Chain Fv-Immunoliposomes
Article Menu

Export Article

Open AccessArticle
Antibodies 2013, 2(2), 338-352; https://doi.org/10.3390/antib2020338

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

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)
View Full-Text   |   Download PDF [588 KB, uploaded 14 May 2013]   |  

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. View Full-Text
Keywords: bispecific antibody; lymphoma targeting; immunotherapy; CD19; CD5 bispecific antibody; lymphoma targeting; immunotherapy; CD19; CD5
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Antibodies EISSN 2073-4468 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top