Abstract

New Ways For Human Antibodies - From Intracellular Applications to Switchable Affinity

Stefan Dübel, Full Professor and Director, Technische Universität Braunschweig

While the generation and optimization of human antibodies by phage display today allows to design fine specificity and kinetic parameters in detail, and CAR-T-cells, ADCs, bi-specific antibodies and many others creative derivatives of the original IgG molecule are approved or in clinical studies, the antibody molecule still offers many opportunities for new and innovative applications.  The access of intracellular antigens with biologicals would add a huge target space to therapeutic antibodies. We used intra-bodies in the first protein knock down mouse to demonstrate the in vivo function of this principle, but also analysed many strategies to insert antibodies from the outside of the cell.  On another end, using cyclic mutants of human calmodulin as an allosteric effector module, antigen binding affinity of different antibodies could be regulated. This allosteric effect was demonstrated for five different scFv fragments under physiological conditions on living cells without the need of pH or ion concentration changes.