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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

Project description

Regulatory T cells therapy for graft versus host disease

Haematopoietic stem cell transplantation (HSCT) is the gold standard treatment for various blood disorders including haematological malignancies. However, in a significant proportion of transplanted individuals the donor's immune system attacks the patient's tissues, a condition known as graft versus host disease (GVHD). Given the role of regulatory T cells in controlling immune responses, the EU-funded TREGeneration project proposes to use donor-derived regulatory T cells as a therapeutic treatment for GVHD. The consortium will investigate different regulatory T cell preparation strategies, determine the necessity of in vitro expansion, and explore the potential benefits of co-administering therapeutic agents. Insight into the mechanisms underlying regulatory T cell therapy will help the treatment of other diseases.

Objective

Our proposal encompasses parallel clinical trials addressing the feasibility and the effectiveness of donor-derived regulatory T cells (Treg) as a therapeutic agent in the treatment and prevention of tissue and organ damage resulting from graft versus host disease (GVHD) after hematopoietic stem cell transplantation (HSCT).
We propose a collaborative clinical study in which Treg therapy for GHVD is the common dominator. However, by bringing together several clinical centers with expertise in this area, we are also having the opportunity to simultaneously address other issues that would not otherwise be addressable by each clinical center on its own. Firstly, by using different Treg preparation strategies, we will be able to determine whether ex vivo isolated Treg are sufficient or whether in vitro expansion and subsequently higher dosages are required. Secondly, we will investigate if sole Treg infusion is effective or if rather co-administration of therapeutic agents that are likely to induce Treg survival and expansion in vivo (rapamycin; IL-2) is required for a successful response to Treg therapy.
The studies on GVHD treatment outcome will be pursued together with a detailed analysis of immune monitoring, comprising T cell receptor clonotype tracking and tissue regeneration markers, in order to further understand the mechanisms underlying the therapeutic and regenerative potential of Treg cells.
Our consortium has developed a concerted approach to the topic of Treg therapy in GVHD. This is a unique opportunity to determine the validity of this cellular immunotherapy approach in GVHD prevention and treatment, with potential for a significant impact on patient quality of life, survival rate and ultimately on the quality of health care provided.

Call for proposal

H2020-PHC-2014-2015

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Sub call

H2020-PHC-2014-single-stage

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Coordinator

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Net EU contribution
€ 1 886 979,18
Address
Avenida prof egas moniz
1649 028 Lisboa
Portugal

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Region
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Activity type
Research Organisations
Links
Other funding
€ 0,00

Participants (8)