What is TREGeneration?
TREGeneration is a research project funded by the European Union's Horizon 2020 Framework Programme for Research and Innovation.
Its full title is "Repair of tissue and organ damage in refractory chronic graft-versus-host disease after hematopoietic stem cell transplantation by the infusion of purified allogeneic donor regulatory T lymphocytes".
The project aims to treat tissue and organ damage associated with acute (aGVHD) and, mostly, chronic graft versus host disease (cGVHD) after hematopoietic stem cell transplantation (HSCT) by the infusion of regulatory T lymphocytes (Treg) purified from the peripheral blood of the original hematopoietic stem cell donor.
To investigate this therapy, five clinical trials are carried out in parallel in Lisbon, Portugal; Boston, USA; Liège, Belgium; Bologna, Italy and Regensburg, Germany.
The work in the project is divided into seven areas:
- Production of Treg infusion products
- Phase I/II clinical trials with donor Treg for steroid-resistant GVHD
- Tissue regeneration and overall immune monitoring after Treg infusion
- Monitoring T cells repertoires by next generation sequencing following Treg infusion
- Statistical analysis of clinical and laboratory data
- Project Management
The project started on January 1, 2015 with a term of 60 months.
On January 1, 2016, we are going to start into the second year of our project.
Main project objectives
- Develop, according to GMP standards, different Treg cell products from HSCT
donors for infusion into patients with steroid-refractory aGVHD and cGVHD
- Evaluate the safety, toxicity and efficacy of infusing different populations of
donor Treg into patients with steroid-refractory aGVHD and cGVHD
- Evaluate the effect of donor Treg infusion in reversal of tissue damage due to aGVHD
- Evaluate the effect of donor Treg infusion on the immune function of patients with
aGVHD and cGVHD
- In vivo tracking of specific TCR clonotypes of naive and memory Treg, CD4+
non-Treg (Tcon) and CD8+ T cells by Next Generation Sequencing in patients with
aGVHD and cGVHD
iMM Lisboa (coordinating institution)
Coordinator: Prof. João Mascarenhas Forjaz Lacerda, MD PhD
The iMM Lisboa is the coordinating institution of TREGeneration. Apart from the overall coordination of the project, they carry out a phase I/II clinical trial of donor Treg administration in steroid-refractory GVHD.
In addition, they are in charge of the workpackage that monitors the tissue regeneration by performing standardized immune monitoring protocols that will evaluate Treg-mediated tissue repair and immunomodulation after infusion.
They are also responsible for managing the dissemination activities of the project.
University Hospital Regensburg
Project leader: Prof. Dr. med Matthias Edinger
The University Hospital of Regensburg carries out two clinical trials, starting recruitment in early 2016:
Phase I/II clinical trial with donor Treg for acute GVHD, and phase I/II clinical trial of in vitro expanded donor naïve Treg administration in steroid-refractory cGVHD.
Prof. Edinger is also in charge of the workpackage that coordinates the production of TREG infusion products at all clinical centers.
Université de Liège, Centre Hospitalier Universitaire Sart-Tilman
Project leader: Prof. Dr. Frédéric Baron
Prof. Baron is in charge of the workpackage that coordinates the clinical trials in all five centers. Its objective is to determine the safety and toxicity of administering donor regulatory T cells to patients with steroid-resistant GVHD.
The Hospitalier Universitaire Sart-Tilman also carries out a Phase I/II clinical trial of donor Treg administration plus rapamycin in steroid-refractory cGVHD (Liège- cGVHD), starting recruitment in early 2016.
University Hospital S. Orsola, Institute of Haematology (Seràgnoli)
Project leader: Dr. Mario Arpinati
Seràgnoli carries out a Phase I-II clinical trial of multiple donor regulatory T cell (Treg) infusions (T reg DLI) for severe refractory chronic graft-versus-host-disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT).
Max Planck Society, Max Planck Institute for Molecular Genetics (MPIMG)
Project leader: Dr. Marie-Laure Yaspo; WP leader: Hans-Joerg Warnatz
The MPIMG is in charge of the monitoring of the T cell repertoires by Next Generation Sequencing (NGS) following Treg infusion. In this workpackage, they characterize and monitor the infused regulatory T cells and T cell repertoire changes in the patients, and they are developing a novel assay to characterize the paired T cell receptor gene repertoires.
Alacris Theranostics GmbH
Project leader: Prof. Hans Lehrach
Alacris Theranostics GmbH is also involved in the NGS workpackage, where they perform the high-throughput sequencing of T cell repertoires in follow-up samples from the patients.
The University of Liverpool
Project leader: Dr. Marta Garcia-Fiñana
In TREGeneration, the University of Liverpool is responsible for the statistical analysis of the clinical and laboratory data. They are going to perform an integrated analysis of Treg infusion effects on GVHD, tissue damage, immune monitoring studies and clonotype tracking. Their goal is to characterize changes over time of tissue damage biomarkers in GVHD patients following Treg-based therapies, to investigate the associations between time-dependent tissue damage biomarkers and clinical data, and to identify both clinical and biological predictors of response to therapy.
GABO:mi mbH & Co. KG
GABO:mi ensures the overall management of the project. It supports the TREGeneration consortium in carrying out its contractual duties, it advises and guides the participants to comply with the EU regulations and with their contractual requirements.
GABO:mi also supports the dissemination, communication and exploitation activities of the project.
Dana-Farber Cancer Institute (Third Party)
Project leader: Prof. Jerome Ritz, MD
The DFCI is involved in TREGeneration as a third party. They carry out a phase I/II clinical trial of donor Treg administration plus low-dose IL-2 in steroid-refractory cGVHD.