Abstract

Targeting the Outside from the Inside with Antibodies

André Frenzel, , Leibniz Universität Hannover

We compared various systems to target intracellular proteins with biologicals, and developed new approaches to achieve this, with the goal to expand the target space of current protein therapeutics. First, we generated the world’s first protein knock down mouse by introducing intrabodies which induce a significant phenotype. This opens up novel perspectives for somatic gene therapy. When linked to our high throughput human monoclonal antibody discovery pipeline, this approach may further facilitate target discovery and validation. Second, our „Sneaking Ligand“ fusion proteins provided a cell-specific delivery of an intracellular regulator of immune activation. Treatment drastically reduced the extravasation of inflammatory cells murine experimental peritonitis and significantly ameliorated the disease course in murine models of rheumatoid arthritis and other autoimmune disease models. Here, in addition to targeting an intracellular protein, the combination of targeting of distinct cell populations with activation stage-dependent effectors promises to improve effectiveness and risk– benefit ratios of therapeutic interventions.