Suicide gene-mediated modulation of graft-versus-host disease.
The development of suicide genes and progress in retroviral gene transfer to T-cells open new perspectives for the treatment of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (BMT) for leukemia and lymphoma. Indeed, suicide genes that metabolize inactive prodrugs into compounds toxic for dividing cells provide a powerful means for the pharmacogenetic control of T-cell reactivity. Here, we demonstrate the selective destruction of activated TK-transgenic T-cells in vivo and develop two new transgenic lines which should be useful for preclinical studies of suicide gene therapy strategies for GVHD.
Cohen
J L
JL
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, CNRS ESA 7087, Groupe Hospitalier Pitié-Salpêtrière, Paris.
Boyer
O
O
Thomas-Vaslin
V
V
Klatzmann
D
D
D000818:Animals; D017209:Apoptosis; D016026:Bone Marrow Transplantation; D015774:Ganciclovir / Q000494:pharmacology; D015316:Genetic Therapy; D006086:Graft vs Host Disease / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D008212:Lymphocyte Depletion / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000637:transplantation; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D013937:Thymidine Kinase; D015774:Ganciclovir