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

Antibodies

Sandra Lüttgau²  Dorothພ Deppe²  Saskia Meyer²  Regina Fertig²  Hossein Panjideh³  Martin Lipp³  Oliver Schmetzer⁴  Antonio Pezzutto⁴  Frank Breitling¹ 

[1] Department Peptide Arrays and Antibody Libraries, Karlsruhe Institute of Technology (KIT), 76344 Eggenstein-Leopoldshafen, Germany;Department of Translational Immunology, German Cancer Research Center and National Center for Tumor Diseases, 69120 Heidelberg, Germany;Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center of Molecular Medicine, 13125 Berlin, Germany;Molecular Immunotherapy, Max-Delbrück Center of Molecular Medicine, 13125 Berlin, Germany

关键词: bispecific antibody;    lymphoma targeting;    immunotherapy;    CD19;    CD5;   

DOI  :  10.3390/antib2020338

来源: mdpi

【 摘 要 】

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 μg/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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.