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HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia

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Science  13 Jun 1997:
Vol. 276, Issue 5319, pp. 1719-1724
DOI: 10.1126/science.276.5319.1719

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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.

  • * To whom correspondence should be addressed at Istituto Scientifico San Raffaele, Via Olgettina, 60, 20132 Milan, Italy. E-mail: bordigc{at}dibit.hsr.it

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