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Science. 1997 Jun 13;276(5319):1719-24.

HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia.

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  • 1Telethon Institute for Gene Therapy (TIGET), Istituto Scientifico H. S. Raffaele, 20132 Milan, Italy.

Abstract

In allogeneic bone marrow transplantation (allo-BMT), donor lymphocytes play a central therapeutic role in both graft-versus-leukemia (GvL) and immune reconstitution. However, their use is limited by the risk of severe graft-versus-host disease (GvHD). Eight patients who relapsed or developed Epstein-Barr virus-induced lymphoma after T cell-depleted BMT were then treated with donor lymphocytes transduced with the herpes simplex virus thymidine kinase (HSV-TK) suicide gene. The transduced lymphocytes survived for up to 12 months, resulting in antitumor activity in five patients. Three patients developed GvHD, which could be effectively controlled by ganciclovir-induced elimination of the transduced cells. These data show that genetic manipulation of donor lymphocytes may increase the efficacy and safety of allo-BMT and expand its application to a larger number of patients.

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PMID:
9180086
[PubMed - indexed for MEDLINE]
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