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
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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.
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(2):338-352.
Lüttgau, Sandra; Deppe, Dorothée; Meyer, Saskia; Fertig, Regina; Panjideh, Hossein; Lipp, Martin; Schmetzer, Oliver; Pezzutto, Antonio; Breitling, Frank; Moldenhauer, Gerhard. 2013. "Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5." Antibodies 2, no. 2: 338-352.