Immune Cell Therapy Shows Promise in Reducing Need for Lifelong Drugs After Liver Transplant

A clinical trial conducted by University of Pittsburgh and UPMC clinician-scientists has reported encouraging results in the quest to reduce liver transplant patients' dependence on lifelong immunosuppressive drugs.

The trial tested an "immune priming" therapy where patients received an infusion of regulatory dendritic cells (DCregs) derived from their donor one week before transplantation.

The Trial and Its Results

The phase I/IIa study, launched in 2017 with funding from UPMC Enterprises, involved 13 living donor liver transplant (LDLT) patients.

One year post-transplant, eligible patients began a process to withdraw immunosuppressive drugs. Of the 13 participants, 8 were eligible for withdrawal. Four achieved complete withdrawal, with three remaining off immunosuppressants for over three years.

This represents a 37.5% rate of tolerating the transplanted organ without immunosuppression in eligible trial recipients. This is compared to a historical rate of about 13% in non-trial adult liver transplant recipients deemed eligible for early withdrawal. The results are reported in the journal Nature Communications.

Background and Significance

Liver transplant recipients typically require lifelong immunosuppressive drugs to prevent organ rejection. Long-term use of these drugs can cause serious side effects including kidney damage, metabolic complications, increased susceptibility to infections, certain cancers, and diabetes.

The liver's unique regenerative properties make living donor transplants possible, allowing a donor to donate a portion of their liver.

Achieving reliable and safe early removal of immunosuppression in a significant percentage of patients is a "huge breakthrough," noting that tolerance has been the "holy grail" of organ transplantation.

Senior author Angus Thomson stated that sparing patients from the serious side effects of immunosuppressive drugs has been a goal pursued by Pittsburgh transplant scientists for three decades.

Important Caveats and Future Steps

The researchers stress that the results are exploratory and not definitive, as the trial was not large enough nor designed to establish efficacy.

The researchers state the findings justify future studies, including a larger randomized control trial. Proposed future research includes:

• Testing a different immunosuppressant medication.
• Administering DCregs after surgery.
• Obtaining DCregs from deceased donors.