Gene Therapy Enables Transplantation Without Immunosuppressive Drugs

Researchers at the University of Pennsylvania Medical Center, working in a rodent model, have succeeded in transplanting livers without the need for immunosuppressive drugs. In a scientific first, a gene therapy strategy was used to alter the donor liver prior to surgery so that the immune system of the recipient became permanently tolerant of the new organ. The new findings are reported in the February issue of Nature Medicine.

Although additional animal studies will be required before human clinical trials of the approach can be considered, the advantages of such a localized system for countering the immune-system rejection of newly engrafted organs are potentially significant. The powerful immunosuppressive drugs now required to allow a life-saving transplanted organ to survive in a recipient's body without rejection do their work only at a substantial cost to the overall well-being of the recipient.

"Currently, all immunosuppression is systemic and lifelong," says Kim M. Olthoff, MD, an assistant professor of surgery and lead author on the study. "So, to protect the new organ from rejection, long-term drugs that suppress the entire immune system must be given, making the person susceptible to infections, cancers, and a number of other complications, including nerve and kidney damage. In our study, a one-time gene therapy treatment of only the donor liver made the recipient's immune system tolerant of the new organ without the need for any further immunosuppression."

The technique developed by the Penn team makes use of an adenovirus -- a virus usually associated with the common cold -- that has been engineered to incorporate the gene that encodes for a protein called CTLA4Ig. The gene-bearing virus, referred to as a vector, is then introduced into an organ preservation solution used to maintain the liver after harvesting and prior to engraftment, resulting in uptake by the organ

Contact: Franklin Hoke
University of Pennsylvania School of Medicine

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