TREGeneration is a clinical research consortium funded by the European Commission's Horizon 2020 Framework Programme for Research and Innovation. Our shared goal is to treat organ damage associated with Graft versus Host Disease (GVHD).
Hematopoietic Stem Cell Transplantation (HSCT) in the main curative treatment for many hematological malignancies. However, despite many advances in the field, GVHD remains a major hurdle to the success of such therapeutic approach. GVHD is a life-threatening condition occurring in about 30-50% of patients undergoing HSCT. GVHD occurs when the donor’s immune system reacts against the tissues of the patient, in an autoimmune-like phenomenon. Mortality is high in patients with intermediate to severe forms of the disease and there is clearly an unmet need for novel treatment strategies that reduce disease burden, with fewer side effects than current therapeutic approaches.
The TREGeneration project tested a cell-based therapeutic approach to treat GVHD in seven parallel Phase I/II clinical trials, where patients were treated with regulatory T cells (Treg), isolated from the blood of the original bone marrow donor. Treg are known to control autoimmunity and have the capacity to suppress immune responses. With these trials the consortium had the following aims:
i) identify the safe dose to be administered and
ii) generate preliminary efficacy data.
Overall, the study encompassed the following overall objectives:
1. Development of different Treg products for infusion into patients with steroid-refractory GVHD.
2. Evaluation of the safety, toxicity and efficacy of donor Treg infusion.
3. Evaluation of the effect of donor Treg infusion on tissue regeneration and immune function of patients.
5. Tracking of lymphocytes in Treg-treated patients through advanced sequencing technology.
The TREGeneration consortium, coordinated by the team of João Lacerda at IMM, Lisbon, Portugal, brings together expertise from five other EU countries: Germany, Belgium, Italy, Spain and the UK, plus a third-party based in Boston, USA. The clinical trials are independently run by each centre, led by:
- João Lacerda at IMM-Lisbon
- Matthias Edinger at UHREG-Regensburg
- Frédéric Baron at CHUST-Liège
- Mario Arpinati at Seràgnoli-Bologna
- José Antonio Pérez Simón at SAS-Seville.
The consortium further includes Marie-Laure Yaspo’s team at the Max Planck Institute for Molecular Genetics, and Hans Lehrach’s team from the SME Alacris Theranostics GmbH, both from Berlin, Germany. The integrated statistical analysis of the data generated by the clinical trials will be performed by Marta García-Fiñana’s team at University of Liverpool, UK.
The results of the clinical interventions and laboratory studies being performed by the TREGeneration consortium have the potential to become a landmark in the field of Hematology and Stem Cell Transplantation, translating to improved patient care, quality of life and survival rate.
