Anti-RBC monoclonal antibodies as a replacement for IVIg and anti-D in ITP

Canada is not self-sufficient for plasma donation for IVIg and only meets 17% of the demand. We need to replace IVIg with a recombinant product (RPA2&5). IVIg is clinically effective in a wide variety of autoimmune and inflammatory states and we have recently shown that monoclonal antibodies specific for mouse erythrocytes can likewise ameliorate five different disease states. To transition to human studies the mechanism of action of the erythrocyte-specific antibodies needs to be confirmed and a large part of this grant is aimed at understanding the mechanism of action of these antibodies. Understanding the mechanism isimportant because the mouse antibodies used cannot be directly used in humans. In addition, we provide a strategy to decrease the adverse event profile of erythrocyte-specific antibodies and design a new antibody construct. Finally we will test selected erythrocyte-specific antibodies in an experimental neuro-inflammatory model. The largest users of IVIg are patients with neuro-inflammatory disease and thus this investigation will be important.

LAZARUS, Alan

Unity Health Toronto

Intramural Research Grant Program

Ontario

$400,000