Global thyTreg Trial Advances Rejection Prevention in Pediatric Heart Transplantation
Gregorio Marañón Hospital has conducted the world’s first clinical trial using thymus-derived regulatory T cells (thyTreg) in children who have undergone heart transplantation. This innovative approach opens a new avenue for preventing immune rejection in pediatric transplant recipients.
Initial results show that a single administration of the cell therapy, delivered a few days after transplantation, is capable of maintaining elevated levels of regulatory T cells (Tregs) for several months. These cells play a key role in promoting immune tolerance toward the transplanted organ.
So far, ten children under the age of two have received the therapy, and six have already completed two years of clinical follow-up after transplantation without experiencing any signs of rejection.
Use of Thymus-Derived Treg Cells in Pediatric Transplantation
The trial focuses on the use of regulatory T cells (Tregs), which are essential for maintaining immune system balance and preventing excessive immune responses. The discovery of these cells and their role in immune regulation were recognized with the 2025 Nobel Prize in Physiology or Medicine.
The study’s main innovation lies in the source of these cells: thymic tissue, which is routinely removed during pediatric cardiac surgery and previously discarded. Researchers obtain highly stable and potent regulatory cells, known as thyTregs, from this tissue. These cells are then isolated, processed, and reinfused into the patient to enhance the body’s natural ability to accept the transplanted organ.
Impact on Immune Tolerance and Safety
Preliminary Phase I/IIa results demonstrate both the technical feasibility and safety of the procedure. During the first six months after surgery—the period associated with the highest risk of acute rejection—treated patients maintained significantly higher levels of Tregs in their blood compared with patients who did not receive the therapy.
In some cases, Treg levels remained above pre-transplant values for up to two years. Furthermore, none of the treated patients developed donor-specific antibodies, a major trigger of immune-mediated rejection.
Although immunosuppressive drugs have dramatically improved transplant outcomes, their long-term use can cause significant side effects, particularly in children. For this reason, Treg-based therapies are considered one of the most promising areas of precision medicine in transplantation. Previous approaches using Tregs obtained from peripheral blood showed limited effectiveness and posed challenges in pediatric patients because of the large blood volumes required.
Using thymus-derived cells may overcome these limitations and provide a more precise and effective method for inducing immune tolerance.
Future Clinical Trials
The team led by Dr. 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 studies.
The next objective is to evaluate whether additional doses of thyTregs can not only maintain protection against rejection but also gradually reduce the need for immunosuppressive drugs without compromising immune stability or graft acceptance.
At the same time, the group is advancing the development of allogeneic thyTreg therapies, which could expand this treatment to adult patients and to children who do not have access to their own thymic tissue.
The research, launched in 2019, has been carried out by the Immunoregulation Laboratory of the Gregorio Marañón Health Research Institute (IiSGM) and the Pediatric Cardiology Department of Gregorio Marañón Children’s Hospital.
The significance of these findings has attracted the attention of leading international institutions, 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 these results at major scientific conferences and meetings.
