Rekombinante Antikörper-Fusionsproteine zur Depletion autoreaktiver B-Lymphozyten

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URI: http://nbn-resolving.de/urn:nbn:de:bsz:21-opus-6255
http://hdl.handle.net/10900/48417
Dokumentart: Dissertation
Date: 2002
Language: German
Faculty: 7 Mathematisch-Naturwissenschaftliche Fakultät
Department: Sonstige - Biologie
Sonstige - Biologie
Advisor: Baeuerle, Patrick A. (Prof. Dr.)
Day of Oral Examination: 2002-09-30
DDC Classifikation: 570 - Life sciences; biology
Keywords: Antikörper , rekombinantes Protein , Autoimmunität
Other Keywords:
antibody , recombinant protein , autoimmunity
License: Publishing license including print on demand
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Inhaltszusammenfassung:

For most autoimmune diseases known, treatment options are very limited. In fact, there is not a single autoimmune indication where a disease-specific treatment regimen has been described. It was the aim of this work to investigate novel strategies for specific depletion of autoreactive B cells as the root cause of many autoimmune diseases. Taken together, this work shows that single-chain fusion proteins can be engineered to target B cells specific for the autoantigen MOG for depletion via immune-effector mechanisms. This was achieved by coupling the MOG extracellular domain to a C-terminally attached effector domain consisting of either an Fc part of human IgG1 or a single-chain variable domain (scFv) directed against CD3e. These proteins induced the efficient depletion of MOG-specific B cells in vitro, ex vivo and in vivo, and thus represent a novel approach for recombinant proteins targeting autoreactive B cells in antibody-mediated autoimmunity. Due to the exacerbating potential of the autoantigen fragment, their use as a therapeutic option in autoimmune conditions requires further development.

Abstract:

For most autoimmune diseases known, treatment options are very limited. In fact, there is not a single autoimmune indication where a disease-specific treatment regimen has been described. It was the aim of this work to investigate novel strategies for specific depletion of autoreactive B cells as the root cause of many autoimmune diseases. Taken together, this work shows that single-chain fusion proteins can be engineered to target B cells specific for the autoantigen MOG for depletion via immune-effector mechanisms. This was achieved by coupling the MOG extracellular domain to a C-terminally attached effector domain consisting of either an Fc part of human IgG1 or a single-chain variable domain (scFv) directed against CD3e. These proteins induced the efficient depletion of MOG-specific B cells in vitro, ex vivo and in vivo, and thus represent a novel approach for recombinant proteins targeting autoreactive B cells in antibody-mediated autoimmunity. Due to the exacerbating potential of the autoantigen fragment, their use as a therapeutic option in autoimmune conditions requires further development.

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