Monoclonal antibodies with anti-D like activity in amelioration of murine ITP

Currently, Canada is not self-sufficient in providing pooled donor derived plasma products (such as IVIg and anti-D) to be used as therapeutics in immune disorders. Anti-D, a red blood cell (RBC) antibody, is one of the first-line treatments for immune thrombocytopenia (ITP) and the only preventative treatment available for hemolytic disease of the fetus and the newborn (HDFN). To overcome supply limitations and meet the growing needs of our population, it is essential to develop anti-D replacements to be used clinically. In an effort to develop such replacements, it is important to first determine the mechanism of anti-D. It has been proposed that anti-D functions to ameliorate ITP through mononuclear phagocytic system (MPS) blockade. This research project aims to delve further into the mechanism and specifically elucidate the role of Fcγ receptors (FcγRs). Using both murine models and in vitro cell culture techniques, the involvement of FcγRs in ITP amelioration by anti-RBC antibodies will be explored. This knowledge can then be utilized in developing a synthetic antibody in a lab which retains similar therapeutic activity as anti-D in ITP and HDFN patients but is free of the associated limitations.

LAZARUS, Alan

Canadian Blood Services

Graduate Fellowship Program

Ontario

$52,000