Through a first-in-human clinical trial of a unique “immune priming” therapy, clinical scientists at UPMC and the University of Pittsburgh have weaned multiple liver transplant patients off all immunosuppressive drugs for more than three years.
Results from a small, early-stage trial are being reported today. nature communications. They confirmed that infusing living donor liver transplant recipients with donor-derived immune cells one week before transplantation and starting removal of immunosuppressive drugs to prevent organ rejection after one year in eligible patients is feasible, safe, and preliminarily effective.
“Long-term use of immunosuppressive drugs can adversely affect the kidneys, cause metabolic complications, and make patients more susceptible to infections, certain types of cancer, and even diabetes,” said lead author Dr. Angus Thomson, Distinguished Professor of Surgery and Immunology at Pitt School of Medicine.
Saving patients from these serious side effects was a goal that Pittsburgh transplant scientists began pursuing 30 years ago under the leadership of the late Dr. Thomas Starzl. We are honored to have achieved this important milestone in making that dream a reality. ”
Angus Thomson, University of Pittsburgh
The liver has a special ability to regenerate. This means that if a healthy person donates part of their liver to someone whose liver is malfunctioning, both parts will regenerate into a complete organ. UPMC leads the nation in living donor liver transplants (LDLTs), with 89 performed through 2025.
However, like almost all organ transplant recipients, LDLT recipients must take lifelong medications to suppress the immune response. Otherwise, your immune system will see the new organ as a foreign invader and attack it. Because patients with end-stage liver disease will die without a new organ, the potentially severe side effects of immunosuppressants are considered tolerable.
But what if a recipient’s immune system could be trained to accept a new organ?
In 2017, with funding from UPMC Enterprises, Thomson and his colleagues, particularly first author Abhinav Humal, MD, clinical director of the Starzl Transplant Institute and chief of UPMC’s transplant division, launched a Phase I/IIa trial to do just that, ultimately recruiting and following 13 LDLT patients.
A few weeks before the transplant surgery, the researchers filtered white blood cells called monocytes from the donor’s blood. These monocytes are then induced to generate regulatory dendritic cells (DCregs), which teach the graft recipient’s immune system to distinguish between foreign invaders and friendly cells.
The donor’s DCreg was then administered to the recipient a week before the transplant surgery, in the hope that it would “tell” the immune system to recognize the donor’s liver as friendly and not attack it.
One year after transplant surgery, recipients were tested to see if they had immunological signals that could help remove immunosuppression without risking organ rejection. Eight of 13 participants were eligible, 4 achieved complete weaning of immunosuppression, and 3 remained off immunosuppressants for more than 3 years.
This implies a transplant organ tolerance rate of 37.5% in trial recipients who are eligible for early withdrawal of immunosuppression after transplantation, compared with approximately 13% in historical non-study adult liver transplant recipients who were deemed eligible for early withdrawal. However, the researchers stressed that while the results were promising, the trial was not large enough and was not designed to establish efficacy, so it was exploratory and not definitive.
“For as long as organ transplantation has been a field of medicine, tolerance has been its holy grail,” Huemer said. “And while we haven’t hit a home run yet, we have certainly gotten on base by reliably and safely removing immunosuppression from a significant proportion of patients early after transplantation. This is a major advance.”
The researchers explained that the results warrant future research, particularly larger randomized controlled trials that would assign half of the transplant patients to receive DCreg and the other half to standard care, allowing true head-to-head comparisons of results. The research team also suggests testing different immunosuppressants than those commonly used, as they may be more effective for DCreg. You may also consider administering DCreg postoperatively to see if outcomes improve, or obtaining DCreg from a deceased donor.
“There are many exciting paths we can take to ensure that our discoveries benefit more patients,” Thomson said. “We are very interested in collaborating with other transplant centers to accelerate and scale our clinical research.”
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Reference magazines:
Humar, A. others. (2026). Donor-derived regulatory dendritic cell infusion and early withdrawal from immunosuppressants in living-donor liver transplantation: a phase I/IIa study. nature communications. DOI: 10.1038/s41467-026-71280-8. https://www.nature.com/articles/s41467-026-71280-8.
