Rekombinante Antikörper-Fusionsproteine zur Depletion autoreaktiver B-Lymphozyten

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.

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.