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SUMMARY:Recombinant HPA-1a antibody therapy for treatment of fetomaternal 
 alloimmune thrombocytopenia - Dr Cedric Ghevaert\, Dept of Haematology\, U
 niversity of Cambridge
DTSTART:20130522T113000Z
DTEND:20130522T123000Z
UID:TALK44586@talks.cam.ac.uk
CONTACT:Sue Griffin
DESCRIPTION:Fetomaternal alloimmune thrombocytopenia\, caused by the mater
 nal 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 mo
 dified 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 B2G1Dnab
  blocks monocyte chemiluminescence by >75%.\n\nIn this first-in-man study\
 , we demonstrate that HPA-1a1b autologous platelets (matching fetal phenot
 ype) sensitized with B2G1Dnab have the same intravascular survival as unse
 nsitised platelets (190 hours)\, whilst platelets sensitized with a destru
 ctive IgG1 version of the antibody (B2G1) are cleared from the circulation
  in 2 hours. Mimicking the situation in fetuses receiving B2G1Dnab as ther
 apy\, we show that platelets sensitized with a combination of B2G1 (repres
 enting destructive HPA-1a antibody) and B2G1Dnab survive three times as lo
 ng in circulation compared to platelets sensitized with B2G1 alone. This c
 onfirms the therapeutic potential of B2G1Dnab. 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 moth
 ers.\n
LOCATION:Lecture Theatre\, Department of Pathology\, Tennis Court Road
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