Descripción del proyecto
Linfocitos T reguladores para tratar la enfermedad del injerto contra el hospedador
El trasplante de células madre hematopoyéticas (TCMH) es el tratamiento de referencia para diferentes hemopatías, incluidas las neoplasias hemáticas. Sin embargo, en una proporción importante de personas trasplantadas, el sistema inmunitario del donante ataca los tejidos del receptor, una afección conocida como enfermedad de injerto contra el hospedador (EICH). Dada la función de los linfocitos T reguladores en el control de las respuestas inmunitarias, el proyecto TREGeneration, financiado con fondos europeos, se propone utilizar linfocitos T reguladores derivados de donantes como tratamiento de la EICH. El consorcio investigará diferentes estrategias de preparación de linfocitos T reguladores, determinará la necesidad de expansión «in vitro» y examinará los posibles beneficios de la coadministración de fármacos. El conocimiento de los mecanismos subyacentes a la terapia con linfocitos T reguladores favorecerá el tratamiento de otras enfermedades.
Objetivo
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.
Ámbito científico
Programa(s)
Convocatoria de propuestas
Consulte otros proyectos de esta convocatoriaConvocatoria de subcontratación
H2020-PHC-2014-single-stage
Régimen de financiación
RIA - Research and Innovation actionCoordinador
1649 028 Lisboa
Portugal