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We will investigate the role endothelial progenitor cells (EPCs) and angiogenesis in myelofibrosis. Besides favouring increased local angiogenesis in the bone marrow, EPCs might also facilitatate ectopic hematopoiesis and, accordingly, EPC mobilization, seeding and proliferation in extramedullary organs might underlie the switch from a relatively dormant, non angiogenic to an actively proliferating, angiogenic and heterotopic myeloproliferative disorder. An exclusive marker of EPCs has not been identified yet, limiting the possibility to therapeutically target these cells. VE-cadherin, an adhesive protein which promotes homotypic cell to cell adhesion and is one of the major components of endothelial cell to cell junctions, is of particular interest since it is expressed by endothelial cells and a subset of EPC only. In previous works we characterized a relatively large set of monoclonal antibodies (mAbs) directed to different epitopes of both human and mouse VE-cadherin. Some of these antibodies presented an exclusive or elevated binding to endothelial cells in angiogenic vessels and circulating EPC. Our objective is to produce radiolabelled VE-cadherin mAbs suitable for in vivo use and define their effect in reducing circulating EPCs and angiogenesis. We will conjugate the mAbs to alpha emitters to be able to selectively kill the target cells without affecting the surrounding tissues.
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