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The mechanism of action of monoclonal antibody blends in the potential replacement of anti-D in HDFN

Principal Investigator / Supervisor: 
LAZARUS, Alan
Co-Investigator(s) / Trainee: 
CRUZ-LEAL, Yoelys
Institution: 
St. Michael's Hospital
Province: 
Ontario
Project Start Date: 
October 1, 2017
Project End Date: 
September 30, 2020
Summary: 
Although polyclonal anti-D has been highly successful at preventing hemolytic disease of the fetus and newborn, a recombinant alternative is long overdue. To design a successful monoclonal antibody (mAb) therapy to replace plasma-derived anti-D, it is important to determine the antibody–mediated immune suppression (AMIS) mechanism. Recently, blends of mAbs targeting different epitopes recapitulated the ‘complete’ AMIS induced by anti-RBC polyclonal antibodies, but the exact mechanism remains unknown. Potential mechanisms for AMIS induced by mAb blends: 1) Steric-hindrance 2) The presence of IgG-Fc regions on the red blood cell (RBC) surface 3) Several antibodies on the RBC surface induce antigen loss on the erythrocyte 4) Deviation of the immune response from the RBC toward the AMIS antibody The aim of this project is to determine if AMIS induced by mAb blends is due to one of these mechanisms. We will use the HOD mouse model of RBC immunization, with RBCs expressing a well-characterized antigen, in combination with a panel of mAbs that recognize different epitopes of the antigen. This work will provide critical knowledge of the mechanism of action of AMIS antibodies to provide a much-needed biological understanding of AMIS mechanisms that will inform the development of a recombinant anti-D therapeutic.
Total Amount Awarded: 
$40,000
Program: 
Postdoctoral Fellowship Program

Projects summaries are contributed by investigators who receive financial support from Canadian Blood Services. The summaries are intended to inform the public of the types of research projects that are supported by our organization. The information described in project summaries should not be considered as recommendation for clinical treatment and diagnosis.