Leiden, July 18, 2021 – Today, Andreas Plückthun’s group at the University of Zurich publishes on Nature Communication with the help of switchSENSE technology. The paper shows that an engineered anti-Her2 tetravalent antibody construct that binds to two different Her2 epitopes (biparatopic) significantly increases the anti-tumoral efficacy over trastuzumab or pertuzumab treatments. The biparatopic tetravalent antibody induces cluster formation of Her2 molecules on the cancer cell surface by its crosslinking capabilities leading to enhanced Her2 growth factor receptor internalization and degradation.

Besides determination of precise binding kinetics of all constructs, the superior distance-dependent crosslinking capabilities of the tetravalent construct over its parental antibody constructs at different Her2 surface densities were measured and quantified by the switchSENSE technology. A Dynamic Biosensors’ internal simulation algorithm confirmed the measured crosslinking effects at different Her2 densities.