Experimental Therapy Helps Liver Transplant Patients Avoid Anti-Rejection Drugs

A small but significant clinical trial has demonstrated that some liver transplant recipients can remain free of immunosuppressive drugs for at least three years following a novel experimental therapy, marking a potential turning point in transplant medicine.

The findings, reported by researchers at the University of Pittsburgh Medical Center and published in the journal Hepatology, stem from a phase 1/2 study involving 12 patients who received liver transplants between 2019 and 2021. All participants underwent a standard deceased-donor liver transplant followed by an infusion of regulatory T cells (Tregs) harvested from the donor and expanded ex vivo. The goal was to induce immune tolerance, thereby reducing or eliminating the need for lifelong immunosuppression.

Of the 12 patients, eight were successfully weaned off all anti-rejection medications within six months to a year post-transplant. As of the most recent follow-up, six of those eight have remained drug-free for at least three years, with no signs of organ rejection or graft dysfunction. The remaining two patients required low-dose immunosuppression due to mild, subclinical immune activity detected through protocol biopsies, but neither experienced clinical rejection.

Immunosuppressive drugs, while essential for preventing organ rejection, carry significant long-term risks including kidney damage, increased susceptibility to infections, and higher rates of malignancy. Eliminating or reducing dependence on these medications could substantially improve quality of life and long-term survival for transplant recipients.

Regulatory T cells are a specialized subset of white blood cells that naturally help maintain immune tolerance and prevent autoimmune responses. In this trial, donor-derived Tregs were isolated, expanded in a controlled laboratory setting, and infused into recipients alongside standard transplant procedures. The approach aims to teach the recipient’s immune system to accept the donor organ as “self,” thereby avoiding the need for chronic pharmacological suppression.

Dr. Angus Thomson, senior author of the study and director of transplant immunology at the University of Pittsburgh, emphasized that while the results are promising, the therapy remains experimental. “We’re seeing durable tolerance in a subset of patients, which suggests that cellular therapy can play a role in reprogramming the immune response after transplantation,” he said. “But we need larger, controlled trials to determine which patients are most likely to benefit and to refine the manufacturing and dosing protocols.”

The study did not include a control group, and all patients received standard baseline immunosuppression immediately after transplant before Treg infusion and gradual tapering. Researchers caution that the approach may not be universally applicable, particularly in cases involving HLA mismatches or prior sensitization, and that long-term monitoring beyond five years will be essential to assess durability and late-onset risks.

Experts in transplant immunology note that while Treg-based therapies have shown promise in preclinical models and early-phase trials for conditions like type 1 diabetes and graft-versus-host disease, their application in solid organ transplantation remains limited. Success in liver transplantation may be partly attributed to the organ’s inherent immunomodulatory properties, which make it more amenable to tolerance induction than other organs such as kidneys or hearts.

The research team is now preparing for a multi-center phase 2 trial that will incorporate randomized controls and expanded biomarker analysis to better predict treatment response. Funding for the next phase is being pursued through the National Institutes of Health’s Human Immunology Project Consortium, with preliminary discussions underway with cellular therapy manufacturers to scale Treg production under good manufacturing practice (GMP) standards.

If future trials confirm these results, Treg therapy could represent a paradigm shift in transplant care — moving from lifelong pharmacological management toward immune system retraining. For now, the approach remains investigational, available only through clinical trials, and not yet approved by regulatory agencies such as the FDA or EMA.