Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats

Lentivirus-mediated gene transfer of viral interleukin-10 delays but does not prevent cardiac allograft rejection

“…This strategy has proven to be effective in adenoviral vector experiments, 20 but in the present study a single (and hence subtherapeutic) (10 mg/kg) dose of CsA administered (by gavage) at the time of transplantation failed to act synergistically with vIL-10 to further enhance allograft survival ( Table 1). The difference in outcome between lentivirus transduction and adenovirus transduction may be ascribed to different kinetics of peak gene expression.…”

“…Amplified cDNA products were run on 1% agarose gels and stained with ethidium bromide. 20 and has been observed with other forms of immunosuppression; prolongation of heart allograft survival, and even permanent acceptance, is not always associated with decreased leucocyte infiltration. 26,27 To analyse in more detail the effect of vIL-10 in the allografts and to seek explanations for the limitation of prolongation of allograft survival to around 2 weeks, the kinetics of vIL-10 in vitro and its effect on a primary alloimmune response were investigated.…”

“…vIL-10 has been delivered to cardiac allografts previously by a variety of plasmids 18 and viral vectors. [19][20][21][22] Its effect on graft survival has been modest and this has been assumed to be due to lack of efficient and sustained gene expression. Nonviral gene vectors generally give low transduction efficiency and oncoretroviral vectors require target cell replication.…”

“…17 Since 1996, a number of groups have used gene therapy to deliver vIL-10 into cardiac allografts in experimental animals using various nonviral plasmid vectors 18 or viral vectors, such as retroviral 19 and adenoviral vectors. [20][21][22] Soluble vIL-10 secreted within the transplanted organ is likely to exert a local in vivo effect at the interface between the immune system and alloantigens, without requiring expression in all target cells. So far, however, expression of vIL-10 within donor cardiac allografts has not led to permanent graft acceptance and prolongation of graft survival has been modest.…”

Gene Therapy Progress and Prospects: Gene therapy in organ transplantation

“…30 In addition, transfer of the gene encoding viral IL-10 delayed graft rejection in a rat model. 31 However, in both these studies, prolongation was extremely modest, and it is therefore unclear what kind of clinical significance can be attached to such results in model systems that are relatively sensitive to tolerance induction.…”