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Cambridge Immunology Network

 

Research

Development of new therapeutics for platelet alloimmune disorders.

This project funded by the NHSBT, looks at developing new diagnostic and therapeutic approaches in the context of fetomaternal alloimmune thrombocytopenia (FMAIT). This is a disease that affects fetuses and newborns, in which the platelet count is decreased by antibodies specific for platelet antigens (fetal Human Platelet Antigen-1a (HPA-1a) ) inherited from the father but which are absent in the mother. FMAIT can result in intracranial haemorrhage and intrauterine death. This disorder affects 1/1200 pregnancies in the UK and leads in 10-20% of fetus/neonates affected to severe brain haemorrhage. We have developed a therapeutic human recombinant high affinity HPA-1a antibody (B2G1Δnab) that competes for binding to the HPA-1a epitope but carries a modified constant region that does not bind to Fc gamma receptors. In the first-in-man study, we demonstrate the therapeutic potential of B2G1Δnab. 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.

 

Publications

Key publications: 
 

Ghevaert C, Herbert N, Hawkins L, Grehan N, Cookson P, Garner SF, Crisp-Hihn A, Lloyd-Evans P, Evans A, Balan K, Ouwehand WH, Armour KL, Clark MR,Williamson LM. Recombinant HPA-1a antibody therapy for treatment of fetomaternal alloimmune thrombocytopenia: proof of principle in human volunteers. Blood. 2013 May 8. [Epub ahead of print]

Ghevaert C, Wilcox DA, Fang J, Armour KL, Clark MR, Ouwehand WH, Williamson LM.Developing recombinant HPA-1a-specific antibodies with abrogated Fcgamma receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia. J Clin Invest. 2008 Aug;118(8):2929-38.

Dr Cedric  Ghevaert
Not available for consultancy

Affiliations

Collaborator profiles: 
Departments and institutes: 
Person keywords: 
pregnancy
alloantibody
human studies