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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

Descrizione del progetto

Terapia con cellule T regolatorie per la malattia del trapianto contro l’ospite

Il trapianto di cellule staminali ematopoietiche è il trattamento standard per diverse malattie che colpiscono il sangue, tra cui le neoplasie ematologiche. Tuttavia, in una percentuale significativa di individui sottoposti a trapianto, il sistema immunitario del donatore attacca i tessuti del paziente, una condizione patologica nota come malattia del trapianto contro l’ospite. Alla luce del ruolo svolto dalle cellule T regolatorie nel controllo delle risposte immunitarie, il progetto TREGeneration, finanziato dall’UE, propone di utilizzare le cellule T regolatorie prelevate dai donatori come trattamento terapeutico per questa patologia. Il consorzio studierà diverse strategie di preparazione delle cellule T regolatorie, determinerà la necessità di espansione in vitro ed esplorerà i potenziali benefici offerti dalla co-somministrazione di agenti terapeutici. La comprensione dei meccanismi alla base della terapia con cellule T regolatorie contribuirà a migliore il trattamento di altre malattie.

Obiettivo

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.

Invito a presentare proposte

H2020-PHC-2014-2015

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Bando secondario

H2020-PHC-2014-single-stage

Meccanismo di finanziamento

RIA - Research and Innovation action

Coordinatore

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES
Contribution nette de l'UE
€ 1 886 979,18
Indirizzo
AVENIDA PROF EGAS MONIZ
1649 028 Lisboa
Portogallo

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Regione
Continente Área Metropolitana de Lisboa Área Metropolitana de Lisboa
Tipo di attività
Research Organisations
Collegamenti
Costo totale
€ 1 886 979,18

Partecipanti (8)