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

Chiara Bonini, Giuliana Ferrari, Simona Verzeletti, Paolo Servida, Elisabetta Zappone, Luciano Ruggieri, Maurilio Ponzoni, Silvano Rossini, Fulvio Mavilio, Catia Traversari, Claudio Bordignon

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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.

Original languageEnglish
Pages (from-to)1719-1724
Number of pages6
JournalScience
Volume276
Issue number5319
DOIs
Publication statusPublished - Jun 13 1997

ASJC Scopus subject areas

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    Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M., Rossini, S., Mavilio, F., Traversari, C., & Bordignon, C. (1997). HSV-TK gene transfer into donor lymphocytes for control of allogeneic graft-versus-leukemia. Science, 276(5319), 1719-1724. https://doi.org/10.1126/science.276.5319.1719