Abstract

Targeting FcRn for therapy: from modulating IgG levels to tumor metabolism

Sally Ward, Professor, Texas A&M 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 engineered antibodies (‘Abdegs’, for antibodies that enhance IgG degradation) can lower the levels of endogenous IgG. Several application areas for the use of Abdegs in therapy and diagnosis will be discussed. FcRn is also known to regulate albumin levels in the body. Tumor cells are dependent on albumin to meet their high demands for nutrients such as amino acids. We have recently 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 indicate a novel function for FcRn as a metabolic regulator.