For the first time, cells obtained from thymic tissue have been used to regulate immune system responses and prevent transplant rejection. Seven infants who underwent heart transplantation have already been treated with this therapy.
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.
This treatment is based on a cellular therapy using thyTreg cells to prevent immune rejection and potentially extend the survival of the transplanted organ indefinitely, thereby prolonging the patient’s life. To date, seven infants who underwent heart transplantation have been successfully treated. Preliminary results suggest that a single administration of this therapy can restore immune balance and may prevent acute organ rejection in these children.
Regulatory T Cells
Recent scientific studies have shown that the immune system possesses an intrinsic regulatory or tolerance mechanism mediated by cells known as regulatory T cells (Tregs), which control and reduce inappropriate inflammatory responses. Various centers worldwide have attempted to harness the regulatory properties of these cells by developing cellular therapies using Tregs obtained from patients’ blood.
Numerous clinical trials conducted to date have demonstrated that this approach is safe when using the patient’s own cells. However, 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 children, although Treg quality is presumed to be superior, the therapy was previously unfeasible due to the extremely low number of Tregs that can be isolated from the small blood volumes safely extracted from pediatric patients.
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 this type of advanced therapy.
Obtaining More Cells from Thymic Tissue
The research conducted by Esther Bernaldo de Quirós and members of Rafael Correa Rocha’s team has led to the development of an entirely 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 characteristics 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.
Ensuring Heart Transplant Viability in Children
This group is pioneering the therapeutic use of thyTreg cells in patients. Together with the Pediatric Heart Unit and the Pediatric ICU at Hospital Gregorio Marañón, they initiated 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 thyTregs 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 patient survival. Because the therapy uses the patient’s own cells, side effects are minimal. The treatment could be implemented in hospitals in the near term, improving transplant outcomes 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 control the immunological mechanisms that could trigger rejection. Importantly, no signs of rejection were detected during the two-year post-transplant period, which is typically associated with the highest incidence of rejection in these patients.
These results were published in the highly prestigious international medical journal Journal of Experimental Medicine.
An “Unprecedented” Advance
Inducing tolerance by “re-educating” the recipient’s immune response through this strategy could address the long-term graft survival challenge, significantly extending life expectancy and offering hope to families facing particularly dramatic clinical situations. The possibility of achieving lifelong graft tolerance would have a profound medical, economic, and social impact.
“We are witnessing an unprecedented medical advance that could establish a new paradigm in the treatment of severe diseases. In the era of advanced cell therapies that are radically transforming the prognosis of cancer patients, our cellular therapy harnesses and enhances intrinsic mechanisms provided by specific immune cells to restore immune tolerance without the use of drugs,” explains Rafael Correa Rocha.
“We firmly believe this therapy could represent a true revolution and may enable 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 obtained so far 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,” he adds.
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 Carlos III Health Institute (ISCIII) and an altruistic donation from the Fundación Familia Alonso. This positions the hospital as a global leader in the use of this therapy.
The potential impact of this therapy on highly prevalent diseases (such as diabetes, rheumatoid arthritis, and transplant rejection) is substantial. It could provide a therapeutic alternative to chronic immunosuppressive drug use — often associated with significant side effects — thereby improving patients’ quality of life.
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