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MICROBOTS

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MICROBOTS – Unravel the power of MICRObial metaBOliTeS to prevent graft versus h...

MICROBOTS – Unravel the power of MICRObial metaBOliTeS to prevent graft versus host disease and cure leukemia relapse Allogeneic stem cell transplantation (allo-SCT) is the most common cellular immunotherapy for hematologic malignancies, but beneficial outcomes are limited by severe morbidity and mortality by graft-vs.-host disease (GVHD) and by... ver más

31/05/2029

KLINIKUM DER UNIVE...

2M€

Presupuesto del proyecto: 2M€

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KLINIKUM DER UNIVERSITAET REGENSBURG 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 2024-02-09

ERC-2023-COG: ERC CONSOLIDATOR GRANTS Scope:Objectives

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1 Participantes

KLINIKUM DER UNIVERSITAET RE...

2.00M€ | Lider

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Duración del proyecto: 63 meses Fecha Inicio: 2024-02-09
Fecha Fin: 2029-05-31

Líder del proyecto

KLINIKUM DER UNIVERSITAET REGENSBURG No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Allogeneic stem cell transplantation (allo-SCT) is the most common cellular immunotherapy for hematologic malignancies, but beneficial outcomes are limited by severe morbidity and mortality by graft-vs.-host disease (GVHD) and by relapse as a consequence of insufficient antitumor immune response (graft-vs-leukemia, GVL). In allo-SCT patients, a diverse gut microbiome is associated with beneficial clinical outcomes and fecal microbiota transplantation (FMT) emerges as a promising therapeutic option for acute gastrointestinal GVHD patients. Yet, how the gut and tissue-associated microbiome governs immune function and tissue homeostasis remains poorly understood. We identified microbial signatures - i.e., configurations of microbial communities and their associated immune-modulatory metabolites - in allo-SCT patients that (i) favourably associate with clinical outcomes, (ii) can engage an Interferon (IFN)-I inducing pathway to induce tissue regeneration, and (iii) protect mice from immune-mediated tissue damage. We therefore hypothesize that gut and tissue-associated microbial consortia and their immune-modulatory metabolites serve as a game changer for allo-SCT. MICROBOTS will test this by (i) providing a thorough characterization of microbiome/metabolome-host interaction at the epithelial interface in allo-SCT patients with or without GVHD, relapse and undergoing FMT and (ii) evaluating the functional impact of identified microbial signatures in advanced preclinical models of GVL and GVHD. These novel insights will provide a template for the design of a Precision FMT approach with defined microbial-metabolite cocktails aimed to achieve robust and durable antitumor responses in allo-SCT patients as well as to improve tissue regeneration and minimize immune-mediated side effects (GVHD). This may induce a paradigm-shift in clinical allo-SCT protocols and potentially other T cell transfer therapies (CAR/TCR T cells) in cancer treatment as a whole.

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