%0 Journal Article
%T Immunotherapy of B-Cell Lymphoma with an Engineered Bispecific Antibody Targeting CD19 and CD5
%A Sandra L¨¹ttgau
%A Doroth¨¦e Deppe
%A Saskia Meyer
%A Regina Fertig
%A Hossein Panjideh
%A Martin Lipp
%A Oliver Schmetzer
%A Antonio Pezzutto
%A Frank Breitling
%A Gerhard Moldenhauer
%J Antibodies
%D 2013
%I MDPI AG
%R 10.3390/antib2020338
%X 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.
%K bispecific antibody
%K lymphoma targeting
%K immunotherapy
%K CD19
%K CD5
%U http://www.mdpi.com/2073-4468/2/2/338