Description du projet
Une approche de médecine de précision pour traiter la septicémie
La septicémie, la réponse extrême de notre organisme face à une infection existante, est une urgence médicale qui peut s’avérer mortelle. Sans un traitement d’urgence, la septicémie peut rapidement entraîner des lésions tissulaires, la défaillance des organes et la mort. Les antibiotiques et les unités de soins intensifs ont grandement amélioré le traitement de la septicémie, et l’on peut espérer que l’immunothérapie continuera d’améliorer les résultats. La mission du projet ImmunoSep, financé par l’UE, consiste à concevoir et à accomplir un essai clinique de validation du principe sur l’immunothérapie personnalisée dans le cas de la septicémie, et à développer une plateforme théranostique de prochaine génération pour mettre en place de futurs essais sur l’immunothérapie personnalisée contre la septicémie. La théranostique est une nouvelle approche qui combine des traitements ciblés spécifiques à partir de diagnostics ciblés spécifiques. La plateforme théranostique du projet en cours reposera sur une analyse multidimensionnelle de la biologie des systèmes des ensembles de données omiques afin d’identifier des biomarqueurs pertinents sur le plan clinique et des cibles thérapeutiques destinées à la médecine de précision.
Objectif
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, and is characterized by a high mortality of up to 30-40%. Treatment of sepsis was revolutionized by two steps that significantly decreased mortality: antibiotics and the intensive care units. It has been hoped that a third revolution, immunotherapy, would further improve outcome of sepsis, but this hope did not materialize. This was due to the incompletely understood pathophysiology, and the heterogeneity of the immune status in different sepsis patients. We propose that while both overinflammation and immunoparalysis are important, they are present in individual sepsis patients.The mission of the present project is to design and perform a proof-of-concept clinical trial of personalized immunotherapy in sepsis, and within this clinical trial, to develop a next-generation theranostics platform for the design of future personalized immunotherapy trials in sepsis. This theranostics platform would be based on an integrated, multidimensional systems biology analysis of omics-based datasets, to identify biomarkers, clinical endotypes, and therapeutic targets for precision medicine approaches. In order to achieve the mission proposed, several complementary aims will be pursued: Aim 1: To design and perform a large personalized immunotherapy trial in sepsis patients, that can provide a clinical answer towards the usefulness of currently employed immunotherapies for sepsis. Aim 2: To chart host genome, epigenome, transcriptome, metabolome and microbiome in at least 180 sepsis patients enrolled in Aim 1 over a defined time course. Aim 3: To use a theranostics approach based on the data provided by Aim 2 to design novel personalized immunotherapeutic strategies. Aim 4: To integrate the clinical and psychological aspects involved when introducing novel immunotherapies for infections in the health care systems of European countries, building bridges with the patient community.
Champ scientifique
- social sciencessociologydemographymortality
- medical and health sciencesclinical medicinecritical care medicine
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantibiotics
- medical and health scienceshealth sciencespersonalized medicine
- medical and health sciencesbasic medicineimmunologyimmunotherapy
Programme(s)
Régime de financement
RIA - Research and Innovation actionCoordinateur
6525 GA Nijmegen
Pays-Bas