Reducing the need for immunosuppressive drugs after transplantation: A research team at Hannover Medical School (MHH) has been awarded €2.4 million to investigate a personalized cell therapy approach. Two researchers from BREATH, the Hannover site of the German Center for Lung Research (DZL), PD Dr. Fatih Noyan and PD Dr. Nikolaus Schwerk, are playing key roles in the project.

A heart or lung transplant can save lives. However, to prevent rejection of the donor organ, patients must take immunosuppressive medication for the rest of their lives. While these drugs are effective, they do not reliably prevent chronic organ rejection and can cause significant side effects.

To reduce the need for immunosuppression and extend graft survival, particularly in children following heart or lung transplantation, a research team at Hannover Medical School (MHH) is developing a personalized cell therapy as part of the AgEndo project.

Instead of broadly suppressing the immune system, the approach aims to use the patient’s own immune cells – known as regulatory T cells (Tregs) – to specifically protect the transplanted organ. This could reduce the need for immunosuppressive drugs, prolong graft function, and ultimately improve the quality of life of affected children and their families. The State of Lower Saxony and the Volkswagen Foundation are funding the three-year project with approximately €2.4 million.

Targeted Immunosuppression at the Site of Transplantation

Tregs are part of the immune system’s natural regulatory mechanisms. By counteracting effector T cells, they help terminate immune responses once infections have been cleared. They also play a key role in preventing autoimmune diseases, in which the immune system mistakenly attacks the body’s own tissues.

Tregs develop in the thymus, an organ located above the heart. During many pediatric cardiac surgical procedures, a small portion of the thymus must be removed to gain access to the heart. The researchers isolate Tregs from this tissue, select and expand them in the laboratory, and prepare them to specifically recognize the transplanted organ. Since these cells originate from the transplant recipient, they are expected to be particularly well tolerated.

Important preliminary research for this innovative therapeutic approach was already conducted as part of a DZL research project led by PD Dr. Fatih Noyan at the BREATH site. The findings from this earlier work provide a foundation for the further development of personalized regulatory T cells in the newly funded AgEndo project.

“We are engineering these personalized Tregs to settle within the transplanted organ. With AgEndo, we are therefore pursuing an approach that uses the patient’s own cells to protect the organ from immune responses directed against the graft, rather than broadly suppressing the immune system,” explains PD Dr. Fatih Noyan from the Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology at MHH and researcher at the DZL site BREATH.

He initiated the project together with PD Dr. Alexander Horke from MHH’s Department of Cardiothoracic, Transplantation and Vascular Surgery. In addition to PD Dr. Noyan and PD Dr. Horke, the project team includes PD Dr. Sybille Landwehr-Kenzel, BREATH Principal Investigator PD Dr. Nikolaus Schwerk, and Prof. Dr. Martin Böhne.

Improving Quality of Life for Children and Their Families

“Donor-specific regulatory T cells have the potential to fundamentally transform transplantation medicine. They offer the prospect of less immunosuppressive therapy and longer graft survival. For affected children and their families, this would mean fewer side effects, fewer hospital stays, and more opportunities to enjoy everyday life without medical concerns,” explains PD Dr. Horke, outlining the vision behind AgEndo.

The findings are intended to lay the groundwork for clinical trials using the newly developed Tregs. In the long term, the approach could also be applied to other types of organ transplantation, autoimmune diseases, and graft-versus-host disease – an immune reaction in which donor T cells attack the recipient’s tissues following bone marrow or stem cell transplantation. MHH is Germany’s largest transplantation center, performing between 300 and 400 organ transplants each year. Transplant recipients range from infants to older adults. However, the number of patients awaiting transplantation far exceeds the number of available donor organs. In Germany alone, approximately 8,200 people are currently waiting for an organ transplant, particularly a kidney, heart, liver, or lung.

Original article: MHH/ Bettina Bandel