Project description
Precision medicine approach to sepsis treatment
Sepsis, the body's extreme response to an existing infection, is a life-threatening medical emergency. Without urgent treatment, sepsis can rapidly lead to tissue damage, organ failure and death. Antibiotics and intensive care units have dramatically improved sepsis treatment, and there is hope that immunotherapy can further improve outcomes. The mission of the EU-funded ImmunoSep project is to design and complete a proof-of-concept clinical trial of personalised immunotherapy in sepsis, and develop a next-generation theranostics platform for future personalised immunotherapy trials in sepsis. Theranostics is a new approach that combines specific targeted therapy based on specific targeted diagnostics. The theranostics platform of the current project will be based on a multidimensional systems biology analysis of omics-based data sets, to identify clinically relevant biomarkers and therapeutic targets for precision medicine.
Objective
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.
Fields of science
- 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)
Funding Scheme
RIA - Research and Innovation actionCoordinator
6525 GA Nijmegen
Netherlands