Gene therapy in transplantation in the year 2000: moving towards clinical applications?

Guillot, Cécile; Cuturi, Maria‐Cristina; Anegón, Ignacio

doi:10.1038/sj.gt.3301083

Cited by 21 publications

(16 citation statements)

References 29 publications

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“…Interleukin 10 (IL-10) is an immunosuppressive cytokine which downregulates Th1 cell response to inflammatory cytokines [1,2]. Increased IL-10 levels have been demonstrated to reduce acute rejection [3,4], but repeated or continuous administration is needed.…”

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confidence: 99%

Electroporation‐mediated interleukin‐10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allografts

Tavakoli

Gazdhar

Pieróg

et al. 2006

The Journal of Gene Medicine

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confidence: 99%

Electroporation‐mediated interleukin‐10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allografts

Tavakoli

Gazdhar

Pieróg

et al. 2006

The Journal of Gene Medicine

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“…Production of these molecules by the graft may allow for more localized rather than systemic effects (although this needs to be specifically evaluated when using secreted molecules), and may also result in an increased bioavailability as a consequence of their continuous production (3). Prolongation of allograft survival has been previously described using gene transfer of immunoregulatory molecules (4 -9).…”

mentioning

confidence: 99%

Prolonged Blockade of CD40-CD40 Ligand Interactions by Gene Transfer of CD40Ig Results in Long-Term Heart Allograft Survival and Donor-Specific Hyporesponsiveness, But Does Not Prevent Chronic Rejection

Guillot

Guillonneau

Mathieu

et al. 2002

The Journal of Immunology

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Previous work on blockade of CD40-CD40 ligand interaction in mice and primates with anti-CD40 ligand mAbs has resulted in a moderate prolongation of allograft survival without the development of true allograft tolerance. In this study, we show in rats that adenovirus-mediated gene transfer of CD40Ig sequences into the graft resulted in prolonged (>200 days) expression of CD40Ig and in long-term (>300 days) survival. Recipients expressing CD40Ig displayed strongly (>90%) inhibited mixed leukocyte reactions and alloantibody production at early (days 5 and 17) and late time points (>100 day) after transplantation, but showed limited inhibition of leukocyte infiltration and cytokine production as evaluated by immunohistology at early time points (day 5). Recipients of long-surviving hearts showed donor-specific hyporesponsiveness since acceptance of second cardiac allografts was donor specific. Nevertheless, long-term allografts (>100 days) displayed signs of chronic rejection vasculopathy. Occluded vessels showed leukocyte infiltration, mainly composed of CD4+ and CD8+ cells, macrophages, and mast cells. These recipients also showed antidonor CTL activity. Recipients expressing CD40Ig did not show nonspecific immunosuppression, as they were able to mount anticognate immune responses that were partially inhibited at early time points and were normal thereafter. We conclude that gene transfer-mediated expression of CD40Ig resulted in a highly efficient inhibition of acute heart allograft rejection in rats. This treatment induced donor-specific inhibition of certain alloreactive mechanisms in the short-, but not the long-term, which resulted in long-term survival of allografts concomitant with the development of chronic rejection.

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“…2 Expression of viral interleukin-10 brought a survival benefit to murine liver or heart allograft than their controls. 3,8 But these viral 2 vectorbased transfer techniques lack efficiency, and there are concerns about viral transmission.…”

Section: Discussionmentioning

confidence: 98%

Non‐viral human IL‐10 gene expression reduces acute rejection in heterotopic auxiliary liver transplantation in rats

et al. 2003

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We studied nonviral delivery, expression, and the effect of the human interleukin-10 (Hu IL-10) gene on the rat model of heterotopic auxiliary liver transplantation (HALT). Two previous pilot studies showed remarkable expression of the Hu IL-10 gene in donor and recipient rats, and a decreasing effect of acute rejection in certain cases. In this study, we focused on the efficacy of Hu IL-10 gene expression to decrease acute rejection compared with cyclosporine A (CyA) in a HALT model. Three study groups and one control group were designed. Each group consisted of 6 DA donor and 6 Lewis recipient rats, which underwent HALT. In the control group, donors and recipients were not treated at all. In group II, recipients were treated with one dose of CyA. In group III, donors were treated with Hu IL-10 plasmid. In group IV, donors were treated with Hu IL-10 plasmid, and recipients were treated with one dose of CyA. Rejection was established by histopathology: it revealed 100% rejection in control and 33.3% rejection in study groups II, III, and IV. Human IL-10 gene expression prevented acute rejection with the same efficacy as CyA in the HALT model in rats.

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Gene therapy in transplantation in the year 2000: moving towards clinical applications?

Cited by 21 publications

References 29 publications

Electroporation‐mediated interleukin‐10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allografts

Electroporation‐mediated interleukin‐10 overexpression in skeletal muscle reduces acute rejection in rat cardiac allografts

Prolonged Blockade of CD40-CD40 Ligand Interactions by Gene Transfer of CD40Ig Results in Long-Term Heart Allograft Survival and Donor-Specific Hyporesponsiveness, But Does Not Prevent Chronic Rejection

Non‐viral human IL‐10 gene expression reduces acute rejection in heterotopic auxiliary liver transplantation in rats

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