First Clinical Trial on Activated Regulatory T Cells: Promising Breakthrough in Preventing the Dreaded Transplant Complication
A team from University Medical Center Mainz and the spin-off ActiTrexx GmbH publishes groundbreaking results from the ATreg-001 trial on the prevention of graft-versus-host disease following stem cell transplantation
Read the German version: Press Release GER | University Medical Center Mainz
ActiTrexx GmbH, a Mainz-based biotech spin-off, in collaboration with University Medical Center Mainz and partners in Dresden, Münster, and Dortmund, has successfully conducted the world’s first clinical trial using so-called activated regulatory T cells (ATregs, Actileucel)—derived from white blood cells of healthy blood donors—to prevent the dreaded graft rejection in patients who have undergone stem cell transplantation. This novel cell therapy aims to prevent the dreaded graft-versus-host disease (GvHD) following an allogeneic stem cell transplant. The Phase I/II study has yielded extremely encouraging results: ATregs can be produced within 24 hours and injected immediately afterward; administration is safe and well-tolerated by patients—a significant step toward a widely available cell therapy. The results have now been published in the journal “Transplantation and Cellular Therapy,” the official publication of the American Society for Transplantation and Cellular Therapy (ASTCT).
A complication that reduces the chances of recovery
Allogeneic stem cell transplantation, in which a patient with a blood cancer receives stem cells from a healthy donor, is the only chance of a cure for many patients with blood cancers. However, acute graft-versus-host disease (aGvHD) poses a high risk associated with the procedure. Immune cells derived from the graft attack the patient’s own protein structures, often with severe consequences for the skin, liver, and intestines. Natural regulatory T cells, which act as the immune system’s “brakes,” can prevent this fatal reaction. However, their widespread clinical use has so far been hindered by the fact that they had to be laboriously isolated from the transplant of a genetically compatible donor and cultured in the laboratory for weeks—a process that is not feasible for most patients.
Activation Instead of Proliferation: The ATreg Principle
The ATreg process developed by ActiTrexx in Mainz takes a different approach. Regulatory T cells (Tregs) are harvested from the blood of healthy, unrelated blood donors and stimulated with a patented activator for 16 hours—without the otherwise standard complex and weeks-long process of cell proliferation in the laboratory. “Early on in the development of the cell therapy, we were able to demonstrate that this activation significantly enhances the natural tolerance-promoting effect of Tregs. As a result, significantly fewer cells are needed to prevent dangerous graft rejection,” explains Prof. Dr. Andrea Tüttenberg, co-founder, CEO, and Medical Director of ActiTrexx GmbH, as well as a researcher at the Department of Dermatology at University Medical Center Mainz. “Since the cells do not have to come from the original transplant donor themselves, but rather from a genetically incompatible third-party donor, ATreg can be produced as needed from a standard blood donation by a healthy, voluntary donor and administered within 24 hours of production—a decisive advantage for the universal applicability of ATreg.”
Results of the First Clinical Trial in Humans
In the multicenter study “ATreg-001” (EU CT Number 2024-516599-14-00), ten patients at sites in Mainz, Dresden, Münster, and Dortmund received the cell therapy approximately ten days after their stem cell transplant, in addition to standard medical treatment. Using a dose-escalation design, three consecutive dose levels were tested. The primary objective of the study was to evaluate the safety and feasibility of this novel procedure.
The results are very encouraging and exceed expectations for an initial safety study: The administration of ATreg itself did not result in any serious side effects during or after the infusion. This was not a given for this preparation derived from genetically mismatched blood donors. All treated patients showed successful engraftment of their stem cell transplant. Furthermore, during the 100-day observation period following transplantation, no patient developed severe Grade 3–4 graft-versus-host disease. No transplant-related mortality was observed either.
“These initial clinical data impressively demonstrate the feasibility and favorable safety profile of ATreg, without the logistically very complex process of cell expansion from genetically compatible donors,” says Dr. Helmut Jonuleit, co-founder and Chief Scientific Officer (CSO) of ActiTrexx GmbH, inventor of the underlying technology, and Director of Research at the Department of Dermatology at University Medical Center Mainz. “As a result, GvHD could become significantly less dangerous in the future, and the search for suitable stem cell donors will also be simplified, since an exact genetic match with the patient becomes less important.”
Outlook
This first Phase I study, involving only a small number of patients, shows promising, encouraging results for a completely new generation of cell therapies. Rapid production without long-term expansion addresses one of the biggest bottlenecks in previous Treg therapies. ActiTrexx views the results as a strong positive signal for further clinical testing of ATreg as a novel cell therapy to prevent GvHD and considers this an important milestone on the path to a more widely available treatment. To demonstrate potential superiority over standard prophylaxis, the next step will be a randomized, controlled follow-up study with a larger and more uniformly treated patient group.
| Original publication
Tuettenberg A, Ruhnke L, Schlöder J, et al. Gp120-Activated Allogeneic Regulatory T cells for Prevention of Graft-versus-Host-Disease – a First-in-Human Trial. Transplantation and Cellular Therapy (2026). DOI: 10.1016/j.jtct.2026.08.054 |
About the Study
ATreg-001 is a prospective, open-label, single-arm, multicenter Phase I/II study conducted at the University Medical Centers of Mainz (LKP Dr. E. M. Wagner-Drouet) and Dresden (Prof. Dr. M. Wermke), as well as at the University Hospital of Münster (Prof. Dr. M. Stelljes) and St. Johannes Hospital in Dortmund (PD Dr. R. G. Meyer). The study was approved by the Paul Ehrlich Institute and the relevant ethics committees and was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. The development of the ATreg procedure was funded by the Federal Ministry of Education and Research as part of the GO-Bio program.
Contact
Prof. Dr. Andrea Tuettenberg
Department of Dermatology
University Medical Center Mainz and ActiTrexx GmbH
email antuette@uni-mainz.de
Press contact
Nadine Berger M. Sc.
Corporate Communications
University Medical Center Mainz
phone +49 (0)6131 – 17 8434
email pr@unimedizin-mainz.de
About the University Medical Center of the Johannes Gutenberg University Mainz
The University Medical Center of the Johannes Gutenberg University Mainz is the only medical institution of supra-maximum supply in the German state of Rhineland-Palatinate and an internationally recognized science location. Medical and scientific specialists at more than 60 clinics, institutes organised in 11 departments work interdisciplinarily to treat around 395,000 patients per year. Highly specialized patient care, research and teaching are inseparably intertwined. Around 3,700 medicine and dentistry students as well as around 600 future medical, commercial and technical professionals are trained in Mainz. With a workforce of approximately 9,000 colleagues the University Medical Center Mainz is one of the largest employers in the region and an important driver of growth and innovation. Find more information online at www.unimedizin-mainz.de