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SELECTBIO Conferences Stem Cells and Antibodies in Drug Discovery Europe 2018

Stem Cells and Antibodies in Drug Discovery Europe 2018 Agenda

Exploiting the Multiple Functions of FcRn for Therapy

E. Sally Ward, Professor, Texas A&M University Health Science Center

The central role of FcRn in regulating IgG persistence and transport provides opportunities for targeting this receptor in multiple different diagnostic and therapeutic situations. The engineering of IgGs with higher affinity for FcRn can be used to produce antibodies with longer in vivo half-lives, but only if the pH dependence of the IgG-FcRn interaction is retained. Conversely, engineered IgGs with increased affinity for FcRn at both acidic and near neutral pH act as potent inhibitors of FcRn. Consequently, such antibodies (‘Abdegs’, for antibodies that enhance IgG degradation) can lower the levels of endogenous IgG. Recent studies in our laboratory have also resulted in the generation of engineered Fc-fusions that selectively clear antigen-specific antibodies (‘Seldegs’, for selective degradation). Recent developments related to the modulation of IgG dynamics will be presented.  We have demonstrated that the loss of expression of FcRn in tumor cells results in increased intracellular albumin accumulation and tumor growth in mouse models. These observations have implications for tumor immunotherapy and indicate a novel function for FcRn as a metabolic regulator.