Development of Soluble FcR-Ig Fusion Proteins

Macrogenics, Inc., Rockville MD

Investigators

Abstract

DESCRIPTION (provided by applicant): The interaction of immune complexes or opsonized cells containing pathogenic autoantibodies with Fc-receptors on effector cells leads to cellular depletion, inflammation and tissue damage depending on the target of the antibody. The current proposal is based on the hypothesis that soluble Fcgamma-receptors (sFcR), by virtue of their ability to block this interaction, can be used to prevent or treat diseases characterized by immune complex deposition or antibody mediated cellular depletion. These sFcR molecules will be made as fusion proteins with a human hinge-Fc segment so that the sFcR will have high avidity and a long serum half-life. The overall aims of this project are the generation of novel sFcR-Ig molecules based on FcgammaRIII (CD16) FcgammaRIIb (CD32b) and FcgammaRIla (CD32a) and the evaluation of these proteins in vitro and in animal models of autoimmune depletion and inflammation. At the end of Phase I one of these proteins will be selected to develop for clinical studies in human subjects as part of Phase II SBIR studies. Idiopathic thrombocytopenic purpura (ITP) is an attractive initial target for an agent blocking the interaction between immune complexes and FcR. We believe that an FcR blockade would also be potentially useful in treating autoimmune hemolytic anemia, lupus, rheumatoid arthritis, Guillain-Barre syndrome and stiff man's syndrome.