Selection, improvement and refinement of immunomodulatory single-chain Fcs to remodel effector f(x)

The advances in the understanding of the biological function, but also in the development of sophisticated manufacturing methods in the recent years have boosted the therapeutic value of Immunoglobulin G class antibodies. Their success is in several cases related to them eliciting effector functions via binding to effector ligand molecules, the canonical and non-canonical Fc receptors. Within this collaborative project, we propose the engineering of a novel single-chain IgG Fc format (scFc) via rational design and directed evolution, to achieve modulated binding to those ligands. Both immunogenic and tolerogenic variants will be developed. To counter possible stability issue, an innovative method of antigen fusion to derive targeted scFc fusion proteins will be explored. An integrative glycoengineering approach will additionally expand the repertoire of the modified scFc by the introduction of novel glycosylation motifs. The overarching goal is to derive a palette of scFcs with good biophysical properties, whose superior immunomodulatory activities can render them Standard-of-Care compounds for diverse areas of disease.