Objective Allogeneic haematopoietic stem cell transplantation (allo-SCT) is the curative option for leukaemia and other haematological tumours. In allo-SCT donor T lymphocytes play a crucial therapeutic role both in providing immunological reconstitution and eradica ting malignant cells. Despite this, the use of donor T cells is limited by the occurrence of fatal graft-versus-host disease (GvHD). A suicide gene codes for a protein able to convert a non-toxic pro-drug into a toxic product. Donor T lymphocytes expressin g the herpes simplex virus-thymidine kinase suicide gene (TK) become sensitive to ganciclovir (GCV) and can be eliminated in the case of GvHD. The aim of this project is to generate TK+ human T lymphocytes that possess substantial anti-leukaemia activity i n vivo. To this I will focus on the response against the HA-1 minor histocompatibility antigen. HA-1 is one of the major targets of immune elimination of leukaemia following allo-SCT, also known as the graft-versus-leukaemia effect (GvL). I will verify in vitro what protocol results in TK+ human T lymphocytes with anti-HA-1 reactivity and test them in vivo for GvL and for GvHD. To this I will treat NOD/scid mice harbouring HA-1+ human leukemias and/or grafted with HA-1+ full-thickness human skin grafts with HA-1-specific TK+ lymphocytes. I will also demonstrate the safety of the treatment, as the possibility to eliminate TK+ cells by GCV administration in vivo. The results of this project will be of paramount importance in the validation of suicide gene ther apy (SGT) as a tool to exploit safe and effective allo-SCT for the cure of haematological and possibly solid tumours. Fields of science medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineemergency medicinegraft versus host diseasemedical and health sciencesclinical medicinetransplantationmedical and health sciencesclinical medicineoncologyleukemia Keywords Adoptive Adoptive immunotherapy Allogeneic Allogeneic haematopoietic stem cell transplantation Leukaemia Minor Minor histocompatibility antigens Suicide Suicide gene therapy cell gene haematopoietic histocompatibility immunotherapy stem therapy transplantation Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-2.1 - Marie Curie Intra-European Fellowships (EIF) Call for proposal FP6-2004-MOBILITY-5 See other projects for this call Funding Scheme EIF - Marie Curie actions-Intra-European Fellowships Coordinator LEIDEN UNIVERSITY MEIDCAL CENTER Address Albinusdreef 2, 2333 za Leiden Netherlands See on map Links Website Opens in new window EU contribution € 0,00
