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Content archived on 2024-06-20

An investigation of host and donor DC modulation in GVHD throught the use of comparative in vitro (human) and in vivo (chimeric human/murine) models

Objective

Allogeneic stem cell transplantation (SCT) still remains the only cure for a variety of malignant, non-malignant haematological diseases and disorders of the immune system. The success of SCT is limitedby post transplant related complications; including li fe threatening infections, relapse of malignantdisease and most notably graft versus host disease (GVHD). It is estimated that between 25-60% sufferfrom GVHD in either its acute or chronic form. Research has implicated the antigen presenting cells(APCs) of the immune system as the initiators of GVHD. Current data suggests that the origin (fromeither patient of donor) of these cells is important. The identification of novel antibodies to APCs anddendritic cells (DC) in particular provide new tools to further the investigation of DC in theimmunobiology of GVHD, and as a consequence a possible role for these novel antibodies for targetedGVHD immunotherapy. Current immunosuppressive prophylaxis is split between traditional drugssuch as cyclosporine and methotrex ate and immunotherapeutics such as antibodies directed againstcertain cell populations. Campath - a CD52 monoclonal antibody has been shown to not only deplete Tcell but also blood DC. T cell depletion is the treatment option for patients with high risk of GVHD,however the disadvantage of such as agent is increased susceptibility to infections and disease relapse.This research aims to use these novel antibodies to further unlock the exact role of host (patient) anddonor DC in GVHD immunobiology. At the same time these antibodies will be compared with acurrent antibody (Campath) in the modulation of GVHD through the use of a human in vitro model ofGVHD and two in vivo chimeric human/murine models of GVHD. This will also provide importantdata for the compariso n of such models in GVHD research with relevance to the clinical pathology.To fulfill this research this fellowship will enable the mobility of a #

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FP6-2002-MOBILITY-6
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Funding Scheme

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IIF - Marie Curie actions-Incoming International Fellowships

Coordinator

UNIVERSITY OF NEWCASTLE UPON TYNE
EU contribution
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Total cost

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Participants (1)

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