First-in-Human Trial Primes Immune System to Accept Donor Livers

4/17/2026

A pre-transplant cell therapy developed at the University of Pittsburgh and tested at UPMC helped several patients go more than three years without immunosuppressant medications.

For more than three years, several patients who received liver transplants from living donors at UPMC have taken none of the daily anti-rejection drugs that typically define life after transplant. A first-in-human clinical trial of immune priming — a strategy in which donor-derived immune cells are infused before surgery to teach the recipient's immune system to accept the new organ — made that possible, according to findings published April 17, 2026, in Nature Communications.

The trial was launched in 2017 with funding from UPMC Enterprises and followed 13 living-donor liver transplant patients. It was designed primarily to test safety and feasibility, not to prove efficacy — but the results offer the strongest evidence to date that this approach may work.

"For as long as organ transplantation has been a field of medicine, tolerance has been its holy grail," said first author Abhinav Humar, M.D., clinical director of the Starzl Transplantation Institute and chief of the Division of Transplantation at UPMC. "And, while we haven't hit a home run yet, we've definitely gotten on base by reliably and safely removing immunosuppression early after transplantation from a significant percentage of patients, which is a huge breakthrough."

In transplant medicine, transplant tolerance is the state in which a recipient's immune system accepts a donor organ long-term without requiring immunosuppressive drugs — a goal that has eluded the field for decades.

How the therapy works

1. The treatment follows a six-step protocol spanning more than one year:

2. Several weeks before surgery, monocytes — a type of white blood cell — are filtered from the living donor's blood.

3. In a laboratory, those monocytes are induced to make regulatory dendritic cells, or DCregs. Unlike immune cells that trigger an attack, DCregs suppress the immune response and help the recipient's system recognize donor tissue as non-threatening.

4. The DCregs are infused into the recipient approximately one week before transplant surgery.

5. The living-donor liver transplant proceeds. Because the liver can regenerate, a healthy donor can give part of their liver and both portions regrow — making this setting especially well-suited to immune-priming research.

6. At one year post-transplant, eligible patients undergo immunological testing to assess whether it is safe to begin reducing their medications.

7. Patients who meet prespecified criteria begin a structured immunosuppression withdrawal protocol.

Results

Eight of the 13 participants were deemed eligible for withdrawal. Four achieved complete withdrawal— three of those four patients have now remained off all immunosuppressants for more than three years, a tolerance rate of 37.5% among eligible patients. That is nearly three times the approximately 13% rate observed historically among similarly eligible adult liver transplant recipients outside a trial.
For those patients, that means years free from the kidney stress, metabolic complications, heightened infection risk, and increased susceptibility to certain cancers that standard anti-rejection therapy can cause.

"Long-term use of immunosuppressive drugs can harm the kidneys, cause metabolic complications, and make patients more susceptible to infections and certain types of cancer, as well as diabetes," said senior author Angus Thomson, Ph.D., D.Sc., Distinguished Professor of Surgery and Immunology in Pitt's School of Medicine. "Sparing patients from these serious side effects has been a goal that Pittsburgh transplant scientists, under the direction of the late Dr. Thomas Starzl, began pursuing three decades ago. It is an honor to achieve this important milestone toward finally realizing that dream."

Starzl performed the world’s first successful liver transplant in a human and is the namesake for the Starzl Transplantation Institute at Pitt, where this research continues today.

UPMC performs more living-donor liver transplants than any other U.S. center, according to UPMC data — 89 in 2025 alone. That clinical volume provided the patient population to test this approach in humans for the first time. Pitt's research laboratories developed and characterized the DCreg manufacturing process; UPMC's transplant program provided the infrastructure to bring it to patients.

What comes next

• The research team has proposed several next steps:

• A larger randomized controlled trial comparing DCregs against standard care

• Testing a different immunosuppressant regimen that may allow DCregs to take effect more reliably

• Administering DCregs after surgery to assess whether timing affects outcomes

• Exploring DCregs derived from deceased donors to expand eligibility

• Pursuing multi-center collaborations to accelerate and scale the findings

• "There are so many tantalizing paths we could take to help our findings benefit many more patients," Thomson said. "We are very interested in collaborating with other transplantation centers to accelerate and scale our clinical research."

Frequently Asked Questions

A: Immune priming is a pre-transplant strategy in which donor-derived regulatory dendritic cells are infused into the recipient before surgery. The goal is to train the immune system to accept the new liver without lifelong anti-rejection drugs.

A: Among eight eligible participants, four achieved complete withdrawal from all immunosuppressant medications. Three of those four have remained drug-free for more than three years. The researchers caution the results are preliminary and require confirmation in larger trials.

A: No. Immune priming is still experimental. The trial was an early-stage safety and feasibility study. Larger randomized trials are needed before it could become part of standard post-transplant care.

Additional Resources

• Published study: Donor-derived regulatory dendritic cell infusion and early immunosuppressive drug withdrawal in living-donor liver transplantation: a phase I/IIa trial in Nature Communications
• Press release: First-in-human trial primes immune system to accept donor livers
• Press contact: Allison Hydzik | UPMC Media Relations
• Related UPMC coverage: Potential for Organ Transplant Without Long-Term Immunosuppression
• Clinical trial registration: DCreg in Living Donor Liver Transplantation | ClinicalTrials.gov
• Multimedia: Headshots of Dr. Angus Thomson and Dr. Abhinav Humar | Credit: UPMC

Authors and Funding

Authors: Abhinav Humar, M.D.; Yannis Hadjiyannis, M.D.; Camila Macedo, M.D.; Lillian M. Tran, M.D.; Beth Elinoff, M.P.H.; Christopher B. Hughes, M.D.; Swaytha R. Ganesh, M.D.; Alan F. Zahorchak, M.S.; Mindi A. Styn, Ph.D.; Adriana Zeevi, Ph.D.; Fadi G. Lakkis, M.D.; Diana M. Metes, M.D., all of Pitt, UPMC or both; Erin M. Ables, M.A., of Indiana University-Bloomington; Douglas Landsittel, Ph.D., University at Buffalo; and Angus W. Thomson, Ph.D., D.Sc., University of Pittsburgh.

Funding and Disclosures: In addition to UPMC Enterprises award #88906, this research was supported by Starzl Transplantation Institute research funds and the Burroughs Wellcome Fund. The National Institutes of Health also provides funding support for related research at Pitt (R01 AI11877, U19 AI131453, U01 AI136779, T32 AI74490, T32 AI089443, P30 DK120531).