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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 411195.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Human antibody RNase fusion protein targeting CD30+ lymphomas
Authors:Menzel, Christian; Schirrmann, Thomas; Konthur, Zoltan; Jostock, Thomas; Dübel, Stefan
Date of Publication (YYYY-MM-DD):2008-04-01
Title of Journal:Blood
Issue / Number:7
Start Page:3830
End Page:3837
Copyright:© 2008 by American Society of Hematology
Review Status:not specified
Audience:Experts Only
Abstract / Description:Targeted RNases (TRs) are immunoenzymes with ribonucleases as cytotoxic effector domains, which are less immunogenic as plant or bacterial toxin components of classical immunotoxins. In this study, we show the generation and production of the first entirely human TR (huTR) directed against CD30+ lymphomas. The scFv-Fc-RNase construct was produced in human embryonic kidney (HEK) 293T cells, yielding up to 4 mg/L soluble protein after purification by protein A affinity chromatography. Size exclusion chromatography revealed a homodimer of the predicted molecular mass. Surface plasmon resonance analysis revealed an affinity to CD30 of KD of less than 1 nM for both the scFv-Fc and the scFv-Fc-RNase proteins. Internalization of the scFv-Fc-RNase protein by CD30+ Karpas-299 cells was demonstrated by confocal microscopy. Proliferation of the CD30+ lymphoma cell line Karpas-299 was strongly inhibited by CD30-specific huTR protein (IC50 = 3.3 nM). The huTR is a promising candidate for the immunotherapy of CD30+ lymphomas because of its expected low immunogenicity, good production yields, and potent effector function upon target cell binding and internalization. Its modular design is set to target other internalizing tumor antigens using different antibody domains.
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Technical University of Braunschweig, Institute of Biochemistry and Biotechnology, Braunschweig
Identifiers:ISSN:1528-0020 [eISSN]
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