Monovalent Fc receptor blockade using novel fusion proteins: The road towards an IVIg replacement

Canada is not self-sufficient for plasma donation for IVIg and only meets 30% of the demand. We need to proactively replace IVIg with a recombinant product. We have proposed that IVIg can be replaced by a recombinant single-chain antibody which binds and blocks Fc receptors involved in autoimmune disease. We successfully designed a monovalent antibody construct which treated mice with the platelet autoimmune disease immune thrombocytopenia (ITP). In this grant we will make a human therapeutic which binds and blocks human Fc receptors. Because single-chain antibodies have a short life in blood, we will fuse these therapeutics to human albumin which has a long life in blood. The first part of this work will be to generate the new therapeutics, test them for efficacy, and then construct the final albumin fusion proteins. We will verify that these therapeutics work in both test tube models as well as in mice repopulated with a human immune system. We will also ensure that the final product does not stimulate any adverse events in our model systems. At the conclusion of this grant we will have developed a therapeutic that can potentially replace IVIg in patients with ITP and potentially other autoimmune diseases.

LAZARUS, Alan

St. Michael's Hospital

Intramural Research Grant Program

Ontario

$400,000