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Selective removal of alloreactive cells from haematopoietic stem cell grafts: graft engineering for GVHD prophylaxis

Koh, MBC; Prentice, HG; Lowdell, MW; (1999) Selective removal of alloreactive cells from haematopoietic stem cell grafts: graft engineering for GVHD prophylaxis. BONE MARROW TRANSPL , 23 (10) 1071 - 1079.

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Abstract

One of the main goals in allogeneic bone marrow transplantation is the abrogation of graft-versus-host disease with the preservation of antileukaemia and antiviral activity. We have established a novel system for the selective removal of alloreactive lymphocytes from donor grafts while retaining an effective allogeneic response to third-party stimulator cells. Initial feasibility studies were done with unrelated HLA-mismatched pairs and then extended into the matched setting. Mononuclear cells from HLA-matched donors were cocultured with irradiated recipient cells prestimulated with cytokines (gamma-IFN and TNF-alpha) in a modified mixed lymphocyte culture (MLC), Alloreactive donor lymphocytes were identified by expression of CD69, an early activation marker and selectively removed by paramagnetic bead sorting. The remaining 'non-alloreactive' lymphocytes were tested in proliferative assays against the original matched recipient and to a third-party donor. A mean depletion of proliferative capacity to 11.5 +/- 9.9% of the original matched recipient response was achieved while the residual third-party response was largely preserved at 77.8 +/- 20.9% which should translate into improved immune reconstitution and preservation of antiviral activity. The non-alloreactive lymphocytes could also possess functional antileukaemia activity. Moreover, the alloreactive cells are easily recoverable in this selective T cell depletion strategy for cryopreservation and ready for immediate access as therapeutic donor lymphocyte infusions in cases of frank relapse post transplant.

Type: Article
Title: Selective removal of alloreactive cells from haematopoietic stem cell grafts: graft engineering for GVHD prophylaxis
Keywords: T cell depletion, alloreactivity, CD69, allogeneic BMT, GVHD, graft-versus-leukaemia, BONE-MARROW TRANSPLANTATION, VERSUS-HOST DISEASE, CHRONIC MYELOID-LEUKEMIA, CHRONIC MYELOGENOUS LEUKEMIA, T-CELLS, CD69 EXPRESSION, DEPLETION, IMMUNOTOXIN, REJECTION, TRANSFUSIONS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology
URI: http://discovery.ucl.ac.uk/id/eprint/128123
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