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Research Group Andreas Plückthun

Keywords

Therapeutic proteins, DARPins, therapeutic antibodies, adenovirus

Summary & Mission statement

We use protein engineering to develop new protein therapeutics especially for cancer, with an emphasis of solving problems that cannot be addressed by more traditional approaches.We exploit the interdisciplinary nature of our laboratory, bridging protein design, structural biology, protein biochemistry, cell signaling and animal work.

Overview

We have developed the ability to rapidly generate highly specific binding molecules to essentially any target, using selection and directed evolution fromsynthetic libraries of Designed Ankyrin Repeat Proteins. The ease of engineering many multispecific formats, tunable half-lives, or chemical derivatization, greatly extends what can be achieved with traditional antibody formats, leading to, e.g., selective induction of apoptosisby several mechanisms as well as other new modes of action. DARPinsare easy to produce, extremely robust and have shown good tolerability in clinical trials. Such projects are carried out from the protein design stage to in vivo efficacy testing.

We have also developed adenovirus as a platform, in which the virus carries no viral genes but genes for multiple secreted therapeutic payloads, in order to produce therapeutics in situin the tumor. The constructed viruses are shielded from the cellular and humoral immune systemby an engineered protein shield and equipped with receptor-specific uptake mechanisms. This strategy allows us to simultaneously deliver multiple genesin vivo, for, e.g., producing therapeutic antibodies fo rcheckpoint blockade, receptor inhibition, or producing cytokines, at thelocation where they are needed.

Publications