Document Detail


Ganciclovir-sensitive acute graft-versus-host disease in mice receiving herpes simplex virus-thymidine kinase-expressing donor T cells in a bone marrow transplantation setting.
MedLine Citation:
PMID:  10708102     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The use of donor T cells expressing the herpes simplex thymidine kinase (HSV-TK) gene followed by ganciclovir (GCV) treatment could allow for specific modulation of the alloreactivity occurring after bone marrow transplantation. We are presently exploring such an approach in a phase I clinical trial. METHODS: To examine the beneficial effect of administrating HSV-TK-expressing donor T lymphocytes +/- GCV treatment on acute graft-versus-host disease (aGVHD) control, irradiated Balb/c or C57BL/6 mice underwent transplantation with allogeneic bone marrow cells in conjunction with CD3+ allogeneic splenocytes from transgenic mice expressing an HSV-TK transgene. GCV treatment was initiated upon the occurrence of severe aGVHD. RESULTS: GCV treatment resulted in a 40-60% long-term survival rate of GVHD-free recipients having received HSV-TK-expressing T cells, whereas only 0-6% of mice survived without GCV treatment. Lethal aGVHD occurred in all the control animals having received non-HSV-TK-expressing T cells, irrespective of GCV treatment. CONCLUSION: Our results demonstrate that the administration of donor HSV-TK-expressing T cells to hematopoietic stem cell graft recipients followed by GCV treatment at the onset of severe aGVHD significantly reduces aGVHD-induced mortality and results in GVHD-free surviving recipients.
Authors:
E Contassot; C Ferrand; R Angonin; J L Cohen; M de Carvalho Bittencourt; F Lorchel; V Laithier; J Y Cahn; D Klatzmann; P Herve; P Tiberghien
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Transplantation     Volume:  69     ISSN:  0041-1337     ISO Abbreviation:  Transplantation     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-23     Completed Date:  2000-03-23     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0132144     Medline TA:  Transplantation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  503-8     Citation Subset:  IM    
Affiliation:
Laboratoire de Thérapeutique Immuno-moléculaire, Etablissement de Transfusion Sanguine, Besançon, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / therapeutic use*
Bone Marrow Transplantation*
Ganciclovir / therapeutic use*
Graft vs Host Disease / mortality,  pathology*,  prevention & control*
Male
Mice
Mice, Inbred BALB C
Mice, Transgenic
Simplexvirus / physiology*
Survival Rate
T-Lymphocytes / enzymology*,  virology*
Thymidine Kinase / biosynthesis*
Chemical
Reg. No./Substance:
0/Antiviral Agents; 82410-32-0/Ganciclovir; EC 2.7.1.21/Thymidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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