Monovalent anti-FcγRI strategy in transfusion medicine

IVIg is clinically effective in a wide variety of autoimmune and inflammatory disorders; however, Canada only meets 17% of IVIg demand. Thus, IVIg replacement with a recombinant product is crucial; and the developing of Fcγ receptor blocking strategies looks promising. Here, we propose to design and to generate a monovalent FcγRI blocker with the potentiality to block autoantibodies and alloantibodies binding to FcγRI on macrophages. This molecule will be useful in the treatment of immune thrombocytopenia and also to avoid hemolytic transfusion reactions in patients who development alloantibodies specific for erythrocytes after receiving multiple red blood cell transfusions, which is one of the unsolved problems in transfusion medicine. Additionally, this monovalent FcγRI blocker should open the way for future IVIg replacement strategies since this platform will allow the construction of more advanced bi-functional therapeutics based on one-arm of the therapeutic blocking FcγRI in conjunction with another arm engaging inhibitory biological pathways.

LAZARUS, Alan

St. Michael's Hospital

Postdoctoral Fellowship Program

Ontario

$162,400