First-of-its-kind Pitt study allows some liver transplant recipients to stop antirejection drugs

For as long as organ transplantation has been practiced, recipients have relied on immunosuppressive drugs to prevent their own immune systems from attacking the new organ as a foreign invader. While these medications are essential for the survival of the graft, they come at a high cost to the patient's overall health. Long-term use can lead to a host of complications, including kidney damage, diabetes, an increased risk of serious infections, and certain types of cancer. The challenge for doctors has always been to balance preventing organ rejection with minimizing these cumulative and often debilitating side effects.

The innovative approach taken by the Pitt researchers involves what they call an "immune priming" therapy. The clinical trial focused on patients receiving a liver from a living donor. A few weeks before the transplant surgery, researchers took white blood cells from the organ donor and used them to grow specialized immune cells known as regulatory dendritic cells. About a week before the transplant, these donor cells were infused into the recipient. The goal was for these cells to "instruct" the recipient's immune system to recognize the incoming liver as friendly, thereby inducing a state of tolerance.

The results of the exploratory study, while based on a small number of patients, are highly encouraging. Of the 13 individuals who participated in the trial, eight were deemed eligible to begin weaning off their immunosuppressant drugs about a year after their transplant. Of those, four were able to stop taking the medications completely. Three of these patients have now been living without any antirejection drugs for more than three years, a significant breakthrough demonstrating the potential for long-term success. One participant, Barbara Bowser, received her transplant in 2018 and has not needed an antirejection pill in over six years.

While the researchers caution that these are early-stage results, the findings justify moving forward with larger studies. The team has applied for funding to conduct a randomized controlled trial to more definitively establish the therapy's effectiveness. Future research will also explore whether the cell infusion can be administered after the transplant surgery. A positive outcome on that front would be a crucial development, as it could allow the therapy to be used for patients receiving organs from deceased donors, who represent the majority of transplant cases. For now, the study stands as a major step toward the "holy grail" of transplantation: achieving organ acceptance without the lifelong burden of immunosuppression.