Protein Engineering Applied to Tumor Targeting

We take a very broad approach to the investigation of tumor targeting, exploiting the protein engineering capabilities we have developed, and to establish rules and principles for designing optimal therapeutics. This also involves the structure and function of the target receptors.

We have been using both our Designed Ankyrin Repeat Proteins (DARPins) and synthetic antibodies in these endeavors. Our high-throughput selection facility gives us access to binders to essentially any target, and through the ability to state-of-the-art modeling, design and directed evolution, we are not limited to existing components, but can generate new ones.

Our focus is on fundamental studies, to understand the interdependencies of affinity, valency, size, stability and effector engineering on in vivo efficacy. This has included many new formats of creating bispecific and multispecific formats, protein-drug conjugates, and new ways of precisely controlling pharmacokinetics.

Another goal is the targeting of specific intracellular proteins and triggering their degradation. We have developed a system for receptor-specific uptake of binding proteins to the cytosol, to achieve two layers of specificity, one for the cell type, one for the target.

Because of the wide range of technologies available in our research group, we can bring projects from biophysical characterization of newly designed proteins, to tests in cell culture, and to measuring biodistribution and efficacy in animal models.