Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia

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• Dr Cedric Ghevaert, Dept of Haematology, University of Cambridge
• Wednesday 22 May 2013, 12:30-13:30
• Lecture Theatre, Department of Pathology, Tennis Court Road.

If you have a question about this talk, please contact Sue Griffin.

Host: Mike Clark (mrc7@cam.ac.uk)

Fetomaternal alloimmune thrombocytopenia, caused by the maternal generation of antibodies against fetal Human Platelet Antigen-1a (HPA-1a) can result in intracranial haemorrhage and intrauterine death. We have developed a therapeutic human recombinant high affinity HPA -1a antibody (B2G1Dnab) that competes for binding to the HPA -1a epitope but carries a modified constant region that does not bind to Fc gamma receptors. In vitro studies with a range of clinical anti-HPA-1a sera have shown that B2G1 Dnab blocks monocyte chemiluminescence by >75%.

In this first-in-man study, we demonstrate that HPA -1a1b autologous platelets (matching fetal phenotype) sensitized with B2G1 Dnab have the same intravascular survival as unsensitised platelets (190 hours), whilst platelets sensitized with a destructive IgG1 version of the antibody (B2G1) are cleared from the circulation in 2 hours. Mimicking the situation in fetuses receiving B2G1 Dnab as therapy, we show that platelets sensitized with a combination of B2G1 (representing destructive HPA -1a antibody) and B2G1 Dnab survive three times as long in circulation compared to platelets sensitized with B2G1 alone. This confirms the therapeutic potential of B2G1 Dnab. The efficient clearance of platelets sensitized with B2G1 also opens up the opportunity to carry out studies of prophylaxis to prevent alloimmunisation in HPA -1a negative mothers.

This talk is part of the Immunology in Pathology series.

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