Investigating the mechanism of anti-CD44 antibody amelioration of IVIg-treatable disease

The intravenous injection of blood serum immunoglobulins (IVIg) is an important medical treatment for many diseases. IVIg is acquired by combining serum antibodies from potentially thousands of blood donors. However, IVIg has several clinical challenges, including high cost, destruction of recipient red blood cells, and theoretical risk of infectious disease transmission. Our laboratory is investigating a new therapeutic called anti-CD44 to replace IVIg. This therapeutic is able to treat many of the same diseases as IVIg. However, it is unclear how anti-CD44 works so many different diseases. We will first investigate anti-CD44 in Immune Thrombocytopenia, where cells called macrophages destroy platelets through a celleating process known as phagocytosis. We will first test how anti-CD44 prevents platelet destruction by determining which step of macrophage phagocytosis becomes blocked. We will also investigate if the signaling within macrophages required to complete phagocytosis has changed following treatment with anti-CD44. We will then use knowledge generated from our research in immune thrombocytopenia to help determine how anti-CD44 works in other inflammatory diseases such as rheumatoid arthritis that are IVIg-treatable. This research will help ensure an affordable and accessible supply of IVIg to Canadians by providing a novel, alternative therapeutic for IVIg-treatable diseases.

LAZARUS, Alan

University of Toronto

Graduate Fellowship Program

Ontario

112333.3