Results from a Phase I/IIa trial show promise for an immune priming approach where donor immune cells are infused into liver transplant recipients before surgery. In the small-scale clinical trial, three patients were reported to remain completely off immunosuppression for over three years thanks to this treatment.
Recipients of organ transplants need to take lifelong medication to prevent the immune system from rejecting the transplant. In the case of end-stage liver disease patients, the serious side effects of immunosuppressants are considered acceptable in the face of a severe and life-threatening condition. Still, researchers have long been looking for strategies to at least reduce the intensity and duration of this treatment, which would significantly improve the health of these patients and the financial burden of long-term immunosuppression.
“Long-term use of immunosuppressive drugs can harm the kidneys, causes metabolic complications, makes patients more susceptible to infections and certain types of cancer, as well as diabetes,” said Angus Thomson, PhD, DSc, professor of surgery and immunology at the University of Pittsburgh’s School of Medicine (UPMC). “Sparing patients from these serious side effects has been a goal that Pittsburgh transplant scientists began pursuing three decades ago. It is an honor to achieve this important milestone toward finally realizing that dream.”
The immune priming approach developed by Thomson’s team makes use of regulatory dendritic cells (DCregs), a type of immune cell that regulate innate and adaptive immunity and have the ability to train the immune system to stop recognizing transplanted cells as foreign. The treatment is made by extracting monocytes from the donor’s blood and inducing them to turn into DCregs.
Launched in 2017, the clinical trial recruited a total of 13 patients who were infused with DCregs from their donor a week before surgery. A year after surgery, transplant recipients underwent a biopsy and an assessment to determine if they were eligible for immunosuppressant withdrawal.
Out of eight patients who stopped taking immunosuppressants, four achieved complete withdrawal and three of them remained off immunosuppression therapy for over three years. These findings represent a significant improvement compared to the rate of patients who successfully withdraw from immunosuppression without intervention, raising it from 16% to 37%.
“For as long as organ transplantation has been a field of medicine, tolerance has been its holy grail,” said Abhinav Humar, MD, clinical director of the Starzl Transplantation Institute and chief of the division of transplantation at UPMC. “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.”
While preliminary efficacy results seem promising, the main objective of this small scale trial was to establish the treatment’s safety and feasibility. Based on these results, a larger scale, randomized trial will be designed and conducted with the purpose of establishing the efficacy of this immune priming approach.
In future studies, the researchers also want to explore the use of an alternative immunosuppressant medication that may be more likely to allow DCregs to stop immune rejection against the transplant, as well as studying the effects of infusing the donor cells after surgery and looking for ways of obtaining these cells from deceased donors to expand the potential applications of this approach.
“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.”
The post Immune Priming Could End Immunosuppression After Liver Transplant appeared first on Inside Precision Medicine.
Modern biology is accelerating at an unprecedented pace, and with it comes increasing complexity. As a result, researchers are shifting toward more patient reflective models, uncovering richer phenotypes, and generating multidimensional datasets that push the limits of traditional workflows. However, become more sophisticated, operational challenges grow. Manual steps introduce variability, workflows don’t scale cleanly across teams or sites, and data pipelines struggle to keep pace with expanding volume and nuance. The result is a familiar bottleneck—ambitious science constrained by throughput, reproducibility, and the significant hands-on time required just to keep experiments moving.
