Gregorio Marañón Completes the World’s First Clinical Trial Using thyTreg Cells in Pediatric Heart Transplant Patients

Gregorio Marañón Hospital has successfully completed the world’s first clinical trial using thymus-derived regulatory T cells (thyTreg) in children undergoing heart transplantation, introducing an innovative therapeutic approach that could open a new pathway for preventing immune rejection in pediatric transplant recipients.

Preliminary results show that a single administration of this cell therapy, delivered a few days after transplantation, can maintain elevated levels of regulatory T cells (Tregs) for several months. These cells play a crucial role in promoting immune tolerance toward the transplanted organ.

According to the hospital, ten children under the age of two have received the therapy so far, and six have already completed two years of post-transplant follow-up. To date, none of them has shown signs of rejection.

The findings suggest that boosting regulatory T-cell levels may help reduce the risk of acute rejection during the most critical period following transplantation.

The trial is based on regulatory T cells (Tregs), a specialized population of immune cells essential for maintaining immune balance and preventing excessive immune responses. The discovery of these cells and their therapeutic applications were recognized with the 2025 Nobel Prize in Physiology or Medicine. The study’s key innovation lies in the source of these cells.

For the first time, researchers have used thymic tissue—routinely removed during pediatric cardiac surgery and previously discarded—to obtain highly stable and potent regulatory T cells.

These cells, known as thyTregs, are isolated, processed, and subsequently administered back to the patient to enhance the body’s natural ability to accept the transplanted organ. Preliminary Phase I/IIa results confirm both the technical feasibility of the procedure and its strong safety profile.

During the first six months after surgery—the period associated with the highest risk of acute rejection—treated patients maintained significantly higher levels of regulatory T cells in their bloodstream compared with patients who did not receive the therapy. In some cases, these elevated levels persisted above pre-transplant values for as long as two years.

Furthermore, none of the treated patients developed donor-specific antibodies, one of the main triggers of immune-mediated rejection, which remains the greatest challenge in organ transplantation.

Although immunosuppressive drugs have dramatically improved transplant survival, their long-term use can cause significant side effects, particularly in children.

In this context, Treg-based cell therapies represent one of the most promising areas of precision medicine in transplantation. Previous trials using Tregs obtained from peripheral blood showed limited efficacy and posed significant challenges in pediatric patients because of the large blood volumes required.

The use of thymus-derived cells may overcome these limitations and provide a more powerful and targeted tool for inducing immune tolerance.

Next Steps: New Clinical Trials

Following these encouraging results, the team led by Rafael Correa, Director of the Immunoregulation Laboratory at Gregorio Marañón Hospital, together with Dr. Manuela Camino, Dr. Nuria Gil, and specialists in Pediatric Cardiac Surgery, is already preparing new clinical trials.

The next objective will be to determine whether additional doses of thyTreg cells can not only sustain protection against rejection but also gradually reduce the need for immunosuppressive drugs without compromising immune stability or graft acceptance.

At the same time, the research group has advanced the development of allogeneic thyTreg therapies, which could extend this treatment to adult patients and to children for whom thymic tissue is not available.

The research, which began in 2019, has been carried out by the Immunoregulation Laboratory of the Gregorio Marañón Health Research Institute (IiSGM) and the Pediatric Cardiology Service of Gregorio Marañón Children’s Hospital.

The significance of these findings has already attracted the attention of leading international institutions and scientific societies, including Harvard University, Massachusetts General Hospital, the Spanish Society of Transplantation, and the Spanish Society of Pediatric Cardiology and Congenital Heart Disease, all of which have invited the research team to present its results at major scientific meetings and conferences in recent weeks.

Read more: europapress.es