Immunological defects after suicide gene therapy of experimental graft-versus-host disease

被引:15
作者
Cohen, JL
Lacroix-Desmazes, S
Charlotte, F
Lejeune, L
Martin, PJ
Klatzmann, D
Boyer, O
机构
[1] Hop La Pitie Salpetriere, UPMC, CNRS, ESA 7087, F-75013 Paris, France
[2] Hop Broussais, INSERM U 430, F-75014 Paris, France
[3] Hop La Pitie Salpetriere, Serv Anat Pathol, F-75013 Paris, France
[4] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA
关键词
D O I
10.1089/10430349950016744
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Donor T cells are beneficial for engraftment, immune reconstitution, and antileukemic effects after allogeneic marrow transplantation, but they also cause graft-versus-host disease. Treatment with ganciclovir can control graft-versus-host disease if donor T cells are genetically engineered to express viral thymidine kinase, Clinical protocols with thymidine kinase-expressing T cells currently prescribe the curative use of ganciclovir for genetic immunosuppression only after clinical manifestations of graft-versus-host disease have appeared. The aim of this work was to compare early/preventive versus delayed/curative treatment of GVHD, Here, we found that ganciclovir administered early after experimental marrow transplantation was highly effective in preventing graft-versus-host disease caused by thymidine kinase-expressing T cells, and surviving recipient mice were able to mount a T cell-dependent B cell response. In contrast, curative ganciclovir administration later after transplantation was much less effective in treating graft-versus-host disease and surviving recipients had markedly impaired immune function. These findings should be considered in the development of future clinical trials using thymidine kinase-expressing T cells; to date, such trials have envisaged the use of GCV to treat only declared graft-versus-host disease.
引用
收藏
页码:2701 / 2707
页数:7
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