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AlloCure

Financiado

Deciphering cellular signalling to cure graft-versus-host disease (GVHD) and leu...

Deciphering cellular signalling to cure graft-versus-host disease (GVHD) and leukemia relapse Acute graft-versus-host disease (GVHD) and leukemia relapse cause 75% of the mortality of patients having undergone allogeneic hematopoietic cell transplantation (allo-HCT). A better understanding of signalling in immune cells, ti... ver más

30/09/2028

UKLFR

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITAETSKLINIKUM FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-06-19

ERC-2022-ADG: ERC ADVANCED GRANTS Scope:Objectives

I+D

Cerrada hace 2 años

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Información adicional privada

No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UKLFR

2.50M€ | Lider

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Duración del proyecto: 63 meses Fecha Inicio: 2023-06-19
Fecha Fin: 2028-09-30

Líder del proyecto

UNIVERSITAETSKLINIKUM FREIBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Acute graft-versus-host disease (GVHD) and leukemia relapse cause 75% of the mortality of patients having undergone allogeneic hematopoietic cell transplantation (allo-HCT). A better understanding of signalling in immune cells, tissue specific cell types and leukemia cells is key to develop novel therapies against GVHD and leukemia relapse. The ambitious overall goal of AlloCure is to identify the pathogenic events that initiate GVHD (1), maintain therapy-refractory GVHD (2) and mediate immune escape causing leukemia relapse (3). To address these high risk/high gain questions novel methods and developments across disciplines are required. (1) I hypothesize that a loss of to date unexplored intestinal enteroendocrine cells promotes GVHD initiation. To study these small cell subsets, we will use reporter genes and novel imaging methods to systematically evaluate their fate and signalling during intestinal GVHD. (2) Signalling propagating refractory GVHD is not well-understood. Our phospho-proteomics data set from corticosteroid- and ruxolitinib-refractory GVHD patients will instruct selective analysis of kinase activation in immune cells and enterocytes by using genetic Cre-lox-based and pharmacological approaches. (3) I have shown that leukemia-derived lactic acid inhibits glycolysis and MEK/ERK signalling in T cells, thereby impairing graft-versus-leukemia (GVL) effects. Here, I will decipher which other leukemia-derived metabolites mediate pathogenic signalling in immune cells and test if oncogenic signalling in leukemia cells drives immunosuppressive metabolite production. To enhance GVL we will inhibit pathogenic kinase activation in leukemia cells and myeloid suppressor cells. Using high risk/high gain approaches in a combination of murine and human studies AlloCure aims to develop individualized therapeutic strategies to interfere with pathogenic signalling responsible for GVHD or leukemia relapse to reduce the mortality rate of patients undergoing allo-HCT.

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