CHU

Allogeneic stem cell transplantation (HSCT) is a curative treatment for a variety of diseases. Viral infections such as Cytomegalovirus (CMV), Epstein-Barr-virus (EBV) and Adenovirus (AdV) are major unsolved problems for patients receiving allogeneic HSCT. Refractory viral infections post-HSCT are rare, life-threatening conditions due to the deficient T-cell response post-SCT and lacking effective treatment options. Protective T-cell immunity could be restored by means of a procedure known as adoptive T-cell transfer. Although cellular immunotherapy is considered a major recent breakthrough in medicine, none of the cellular treatment approaches has yet become a standard treatment. The reason for this limited translation into daily clinical practice is the lack of controlled, prospective clinical trials investigating efficacy of immunotherapy. The objective of TRACE is to bring adoptive T-cell transfer into clinical routine as a life-saving, curative and safe treatment for refractory viral infection post-HSCT. TRACE is a multi-national clinical trial to prove efficacy and safety of adoptive T-cell transfer in immune-compromized individuals. For the first time, this trial will show that a unique individualized immunotherapy could be included into evidence based clinical routine in rare diseases. Regulatory and structural hurdles will be overcome by standardized GMP-procedures. It will be a major milestone in the development of medicine and health economics to bring such a unique personalized treatment approach into a clinical efficacy trial. The consortium provide excellence in immunotherapy through partners from basic, clinical and industrial research and GMP facilities, with proven qualification and expertise in the field of HSCT, GMP manufacturing and adoptive T-cell transfer. It will bring medicine towards physiological self-protection of the human body instead of cost-intensive toxic agents and will thereby improve survival and quality of life.

Immune-mediated diseases (IMIDs) are an increasing medical burden in industrialized countries worldwide. IMIDs are characterized by an enormous heterogeneity with regard to disease outcome and response to targeted therapies, which currently cannot be adequately anticipated to tailor individual patient management. Hence, mechanistic understanding of this heterogeneity and biomarkers predictive for disease control and therapy response over time are important prerequisites of a future precision medicine in IMIDs. ImmUniverse has been formed as a European transdisciplinary consortium to tackle these unmet needs and to understand the role of the crosstalk between tissue microenvironment and immune cells in disease progression and response to therapy of two different IMIDs: ulcerative colitis and atopic dermatitis. Following this unique cross-disease approach ImmUniverse will fill the gap and the limitations of current studies, which do not systematically compare the complex interactions between recirculating immune cells and the respective tissue microenvironment. The consortium will combine analysis of tissue-derived signatures with “circulating signatures” detectable in liquid biopsies, employing state-of-the-art profiling technologies corresponding to multi-Omics datasets. The project will also bring diagnostics in IMID to a new level by implementing disruptive non-invasive liquid-biopsy methodology in combination with novel, validated circulating biomarker assays which are expected to improve diagnosis, inform early in the clinical course on disease severity and progression and enable treatment response monitoring. The identified signature will be validated to monitor state/progression and response to therapy in prospective observational cohorts. Realization of these objectives will result in improvement of patient management, lead to increased patient well-being and will significantly reduce the socioeconomic burden of these diseases.

3TR is a transdisciplinary consortium made of experts in all areas of medicine, basic sciences and bioinformatics from academic institutions, SMEs, and 8 major pharmaceutical companies, teamed to study a fundamental issue in medicine: the mechanisms of response and non-response to therapies, the major aim of 3TR, both within single disease entities and across diseases, where molecular stratification may identify shared disease taxonomies. The molecular identification of groups of patients to whom a drug will benefit, will allow focusing on those who are drug orphan. Harmonization of data from existing academy or industry-sponsored studies will identify biomarkers to inform a new collection. Specimens of diseased tissues, blood, stools, and other fluids will be obtained in a de novo observational prospective trial with standard of care medication prior, during and after first or second line of treatment. Because the studies will be at different phases of progression, a carrousel model of work was designed for input and output of data to be continuously analysed, and interpreted, to inform those measurements to be undertaken and allow cross-validation of results. The 3TR team will elucidate the role of the microbiome, genetics and regulatory genomic features in disease progression. The working aims of 3TR are: 1) establish a centralized data management platform; 2) perform comprehensive molecular and clinical characterisation of a prospective patient cohort; 3) establish integrated analysis of all data using advanced bioinformatics/statistical and modelling methods; 4) identify sets of predictive biomarkers of response/non-response to therapies; 5) improve the competitiveness of European industry and support development of novel solutions. 3TR will sustain beyond the project end the samples and its knowledge base. 3TR will challenge and revolutionize the conventional single-disease based approach with important implications in future disease treatment.