The modular nature of antibodies allows the design of antibody-related formats with tailored characteristics. The antibody’s Fc part, encompassing the effector functions, represents an attractive scaffold for engineering therapeutic molecules as demonstrated by the generation of Fcabs (Fc domain with antigen-binding sites). By engineering the C-terminal loops (AB, CD and EF loop) in the CH3 domains, two antigen binding sites can be inserted in close proximity.

The study presented in this webinar deals with the determination of the first X-ray structures of three Fcabs that differ in loop design, specificity, affinity and thermal stability and reveals their overall structural integrity and native fold.

Furthermore, by investigation of the interaction of these Fcabs with their respective antigens (HER2 or VEGF) using a set of complementary techniques (X-ray crystallography, size exclusion chromatography combined with multi-angle light scattering [SEC-MALS], isothermal titration calorimetry [ITC], fluorescence correlation spectroscopy [FCS]), insights into the binding modes and binding stoichiometries were gained.