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

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 Epstei...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1997-06, Vol.276 (5319), p.1719-1724
Main Authors: Bonini, Chiara, Ferrari, Giuliana, Verzeletti, Simona, Servida, Paolo, Zappone, Elisabetta, Ruggieri, Luciano, Ponzoni, Maurilio, Rossini, Silvano, Mavilio, Fulvio, Traversari, Catia, Bordignon, Claudio
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Biopsies
Blood
Body Weight
Bone marrow
Bone Marrow Transplantation - adverse effects
Cells
Chronic myeloid leukemia
Combined treatments (chemotherapy of immunotherapy associated with an other treatment)
Donors
Ganciclovir - therapeutic use
Gene Transfer Techniques
Genetic Therapy
Graft vs Host Disease - etiology
Graft vs Host Disease - therapy
Humans
Leukemia
Leukemia - immunology
Leukemia - therapy
Leukocytes
Lymphocyte Transfusion
Lymphocytes
Lymphocytes - enzymology
Lymphoma, Non-Hodgkin - therapy
Lymphoproliferative Disorders - therapy
Medical research
Medical sciences
Myeloid leukemia
Patients
Persistence
Pharmacology. Drug treatments
Pilot Projects
Relapse
Simplexvirus - enzymology
Simplexvirus - genetics
Suicide
T lymphocytes
Thymidine Kinase - genetics
Transplantation, Homologous
Transplants & implants
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.276.5319.1719