Gene transfer of cytoprotective and immunomodulatory molecules for prevention of cardiac allograft rejection

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Serval ID
serval:BIB_607CA3C6C298
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Gene transfer of cytoprotective and immunomodulatory molecules for prevention of cardiac allograft rejection
Journal
European Journal of Cardio-Thoracic Surgery
Author(s)
Vassalli  G., Fleury  S., Li  J., Goy  J. J., Kappenberger  L., von Segesser  L. K.
ISSN
1010-7940 (Print)
Publication state
Published
Issued date
11/2003
Volume
24
Number
5
Pages
794-806
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Nov
Abstract
Current treatments of heart transplantation are limited by incomplete effectiveness, significant toxicity, and failure to prevent chronic rejection. Genetic manipulation of the donor heart at the time of removal offers the unique opportunity to produce a therapeutic molecule within the graft itself, while minimizing systemic effects. Cytoprotective approaches including gene transfer of heme oxygenase (HO)-1, endothelial nitric oxide synthase, and antisense oligodeoxynucleotides specific for nuclear factor (NF)-kappa B or intercellular adhesion molecule (ICAM)-1 reduced ischaemia-reperfusion injury and delayed cardiac allograft rejection in small animals. Exogenous overexpression of immunomodulatory cytokines such as interleukin (IL)-4, IL-10 and transforming growth factor-beta, as well as gene transfer of inhibitors of pro-inflammatory cytokines also delayed graft rejection. Gene transfer-based blockade of T-cell costimulatory activation with CTLA4-Ig or CD40-Ig resulted in long-lasting graft survival and donor-specific unresponsiveness, as manifested by acceptance of a second graft from the original donor strain but rejection of third-party grafts. Similar results were obtained with donor major histocompatibility complex class I gene transfer into bone marrow cells. Gene therapy approaches to chronic rejection included gene transfer of HO-1, soluble Fas, tissue plasminogen activator and antisense oligodeoxynucleotides specific for the anti-apoptotic mediator Bcl-x or the E2F transcription factor. Despite major experimental advances, however, gene therapy for heart transplantation has not entered the clinical arena yet. Fundamental questions regarding the most suitable vector, the best gene, and safety issues remain unanswered. Well-controlled studies that compare gene therapy with established treatments in non-human primates are needed before clinical trials can be started.
Keywords
Animals Cytokines/genetics Cytoprotection/genetics Forecasting Gene Therapy/*methods *Gene Transfer Techniques Graft Rejection/*prevention & control *Heart Transplantation/immunology Humans
Pubmed
Web of science
Open Access
Yes
Create date
15/02/2008 11:29
Last modification date
25/09/2019 6:09
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