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Optimization of monoclonal anti-erythrocyte antibodies for improved immunoprophylaxis in a murine model

Principal Investigator / Supervisor: 
LAZARUS, Alan
Co-Investigator(s) / Trainee: 
NI, Heyu
Institution: 
St. Michael's Hospital
Province: 
Ontario
Project Start Date: 
October 1, 2017
Project End Date: 
September 30, 2019
Summary: 
Donor-derived anti-D prevents hemolytic disease of the fetus and newborn by a process known as antibody-mediated immune suppression (AMIS). It is highly desirable to replace donor-derived anti-D with a monoclonal antibody, however the mechanism(s) of AMIS remains unclear. In this application we propose to examine mechanisms of AMIS induction in a full murine model. We have preliminary data indicating that the Fc region of the AMIS IgG drives AMIS activity and objective 1 will therefore determine and substantiate if AMIS-induction is dependent upon the Fc region of IgG. The IgG Fc region has a single glycosylation site which controls IgG immune functions and can fine-tune IgG immune activities. Objective 2 will first examine if absolute Fc glycosylation is important for AMIS activity. Then we shall generate IgG Fc glycan isoforms (each known to be optimal for different activating/inhibitory functions) to determine if selected major glycan isoforms can be used to optimize IgG AMIS activity. Finally, some monoclonal AMIS antibodies can suppress while others enhance the immune response. Objective 3 is focused on understanding which attributes of an AMIS antibody contribute to “suppression” versus “enhancement” to avoid enhancement which has unfortunately occurred in some patients treated with monoclonal anti-D antibodies.
Total Amount Awarded: 
$400,000
Program: 
Intramural Research Grant 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.