Description du projet
Traitement par lymphocytes T régulatrices de la maladie du greffon contre l’hôte
La transplantation de cellules souches hématopoïétiques constitue le traitement de référence pour diverses maladies du sang, dont les hémopathies malignes. Cependant, dans une proportion importante de transplantations, le système immunitaire du donneur attaque les tissus du patient, ce que l’on appelle la maladie du greffon contre l’hôte (GVHD). Fort du rôle que les lymphocytes T régulateurs jouent dans le contrôle des réponses immunitaires, le projet TREGeneration, financé par l’UE, propose d’utiliser des lymphocytes T régulateurs dérivés de donneurs comme traitement thérapeutique de la GVHD. Le consortium étudiera différentes stratégies de préparation des lymphocytes T régulateurs, déterminera la pertinence d’une expansion in vitro et explorera les avantages potentiels de l’administration conjointe d’agents thérapeutiques. La compréhension des mécanismes qui sous-tendent la thérapie par lymphocytes T régulateurs contribuera au traitement d’autres maladies.
Objectif
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.
Champ scientifique
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RIA - Research and Innovation actionCoordinateur
1649 028 Lisboa
Portugal