A Therapy Based on Thymic-Derived thyTreg Cells
Researchers from the Immunoregulation Laboratory at Hospital General Universitario Gregorio Marañón, a public hospital in the Community of Madrid, have developed a treatment that is unique worldwide. The therapy is based on a cellular approach using thymic-derived thyTreg cells to prevent immune rejection and potentially extend the survival of transplanted organs indefinitely, thereby prolonging patients’ lives.
To date, seven infants who underwent heart transplantation have been successfully treated. Preliminary results suggest that a single administration of this therapy is capable of restoring immune balance and may prevent acute organ rejection in these children.
Developed entirely at Hospital Gregorio Marañón, the therapy uses cells obtained from thymic tissue to regulate immune responses and prevent rejection in pediatric heart transplants. The treatment has been well tolerated, with no adverse effects associated with the administration of thyTreg cells, and no signs of rejection have been observed in any of the treated children.
In the first patient, a single infusion administered one week after transplantation preserved proper immune balance for two years — the period associated with the highest incidence of rejection in this type of patient.
Regulatory T Cells and a New Source: The Thymus
Recent scientific studies have demonstrated that the immune system possesses an intrinsic regulatory or tolerance mechanism mediated by regulatory T cells (Tregs), which control and reduce inappropriate inflammatory responses. Various centers worldwide have attempted to harness these cells by developing therapies using Tregs obtained from patients’ blood.
Although numerous clinical trials have confirmed the safety of using autologous Treg cells, the expected therapeutic efficacy has not been achieved due to the limited quantity and reduced functional quality of “aged” Tregs obtained from adult blood. In pediatric patients, although Treg quality is presumed to be superior, therapy was previously unfeasible due to the extremely low number of Tregs that can be isolated from the small blood volumes safely extracted from children.
For the past ten years, the Immunoregulation Laboratory at the Gregorio Marañón Health Research Institute (IISGM), led by Rafael Correa Rocha, has investigated how to obtain large quantities of high-quality Tregs from an alternative source to blood, enabling pediatric patients to access advanced cell therapies.
The research led by Esther Bernaldo de Quirós and the team has resulted in a completely new strategy to manufacture therapeutic doses of Treg cells from the thymus — a tissue that covers the heart and is routinely discarded during pediatric cardiac surgeries. Tregs derived from thymic tissue (thyTregs) possess unique properties and an exceptionally high regulatory capacity. The protocol developed by the group allows for the production of thousands of times more cells than can be obtained from blood.
A Pioneering Clinical Trial
This team is pioneering the therapeutic use of thyTreg cells in patients. In collaboration with the Pediatric Heart Unit and the Pediatric ICU at Hospital Gregorio Marañón, they launched a clinical trial three years ago evaluating thyTreg therapy to prevent rejection in infants undergoing heart transplantation.
This trial is the first worldwide to administer Treg therapy in transplanted children and, notably, the first to use thymic-derived thyTreg cells in humans instead of blood-derived Tregs. This approach enables the use of a significantly higher number of cells of superior quality, making advanced cell therapy feasible in pediatric patients.
This therapeutic strategy may restore proper immune balance and could completely inhibit or significantly reduce the immune responses responsible for rejection, potentially extending graft viability indefinitely and thereby prolonging patients’ lives. Because the therapy uses the patient’s own cells, side effects are minimal. It could be implemented in hospitals in the near term, improving transplant survival rates in a country that leads the world in organ donation and transplantation.
Irene, the First Patient
Six-month-old Irene was born with a congenital heart condition requiring heart transplantation and became the first patient worldwide to receive this innovative therapy following her transplant at Hospital Gregorio Marañón.
One week after transplantation, she received a single dose of her own thyTreg cells and was closely monitored for two years to determine whether the therapy could reduce the risk of rejecting her new heart.
During this period, Irene showed higher circulating levels of Treg cells compared to pediatric heart transplant recipients who did not receive thyTreg therapy. The presence of these cells helped maintain control over the immunological mechanisms that could trigger rejection.
Importantly, no signs of rejection were detected during the two-year post-transplant period — the time frame associated with the highest incidence of rejection in these children. These results were recently published in the prestigious international journal Journal of Experimental Medicine.
An Unprecedented Medical Advance
“ We are witnessing an unprecedented medical advance that could establish a new paradigm in the treatment of severe diseases,” explains Rafael Correa Rocha, Director of the Immunoregulation Laboratory.
“In the era of advanced cell therapies that are radically transforming the prognosis of cancer patients, our therapy harnesses and enhances intrinsic mechanisms provided by specific immune cells to restore immune tolerance without the use of drugs. We firmly believe this approach could represent a true revolution, enabling effective treatment of serious conditions such as transplant rejection, autoimmune diseases, graft-versus-host disease, and even hyperinflammatory syndromes responsible for many ICU admissions due to respiratory distress. The initial results confirm the therapy’s safety and suggest it may be highly effective in controlling unwanted immune responses, positioning our country at the forefront of this major clinical breakthrough.”
Commitment to Independent Clinical Research
The entire process — from preclinical research to therapeutic application in patients — has been developed entirely within the Immunoregulation Laboratory at Hospital Gregorio Marañón, with financial support from the Instituto de Salud Carlos III and an altruistic donation from the Fundación Familia Alonso.
The potential impact of this therapy on highly prevalent diseases (such as diabetes, rheumatoid arthritis, and transplant rejection) is substantial. It could provide an alternative to the chronic use of immunosuppressive drugs — often associated with significant side effects — thereby improving patients’ quality of life.
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