Better control and treatment of immune-mediated diseases by exploring the universe of microenvironment imposed tissue signatures and their correlates in liquid biopsies

Informations projet

ImmUniverse

N° de convention de subvention: 853995

DOI

10.3030/853995

Projet clôturé

Date de signature de la CE 17 Decembre 2019

Date de début 1 Janvier 2020

Date de fin 30 Juin 2026

Financé au titre de

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coût total

€ 31 110 000,00

Contribution de l’UE

€ 15 500 000,00

Coordonné par

UNIVERSITA HUMANITAS
Italy

Periodic Reporting for period 5 - ImmUniverse (Better control and treatment of immune-mediated diseases by exploring the universe of microenvironment imposed tissue signatures and their correlates in liquid biopsies)

Période du rapport: 2024-01-01 au 2024-12-31

Résumé du contexte et des objectifs généraux du projet

ImmUniverse aims to advance the understanding of the molecular mechanisms underlying Ulcerative Colitis (UC) and Atopic Dermatitis (AD) by implementing a multi-omics approach using a broad range of molecular profiling techniques to identify signatures of local and circulating biomarkers and mechanistic principles that are informative of disease severity and future disease progression. The overall concept of identifying integrated comprehensive molecular signatures of disease-affected tissue microenvironment and matched blood biosamples over time will be supplemented with disruptive non-invasive liquid-biopsy methodologies to ultimately reduce the reliance on invasive biopsy methods. ImmUniverse aims to significantly optimize immune-mediated inflammatory disease (IMID) management and consequently to improve every patient’s life. Following this unique and unparalleled approach, ImmUniverse will fill the gap and the limitations of previous investigational approaches, which did not shed light into the complex interactions between circulating immune cells and tissue microenvironment. In addition, due to the parallel study of two different IMIDs, the project will enable the identification of both disease-specific as well as cross-disease signatures and underlying pathological pathways. ImmUniverse will provide a scalable, clinic-ready production infrastructure for delineating the tissue microenvironment and accessible matrices, such as blood and stool, using multiple technologies (single cell sequencing, multi-omics approaches) on several molecular Omics layers.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The Consortium has made significant progress in enhancing its infrastructure to support integrative data analysis. This includes the implementation of a robust computational platform, which houses a diverse array of clinical and experimental datasets, as well as advanced visualization and prediction tools. In addition, comprehensive disease maps for UC and AD have been finalized, further advancing the project's capabilities in understanding these complex conditions. The maps are freely available for online browsing for the research community via https://imi-immuniverse.elixir-luxembourg.org. Prospective data analysis has taken off with the completion of different omic layers of the Deep Personal Profiling (DPP) cohort, while analyses beyond DPP is currently ongoing. Dissemination of DPP results is underway.
Regarding retrospective studies, UC and AD biomaterial analysis has initiated, generating Omics data at different levels from blood/serum, biopsies and FFPE tissue samples across the entire Consortium.
The mapping and transformation of four retrospective cohorts and the UC and AD prospective data into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) is completed.
Currently, 68% of patient recruitment has been achieved for AD, with 202 out of 300 patients enrolled, Meanwhile, the recruitment target for ulcerative colitis (UC) has been fully met, with 270 patients enrolled.Two new clinical sites that have joined the Consortium contribute to increase AD recruitment efforst .
dOFM as non-invasive liquid biopsy technology for AD is actively recruiting (12 patients included) and an interim report has been circulted with preliminary data generated. Moreover, retrospective data from a previous dOFM study has been made available to ImmUniverse and is currently being integrated to provide robust data. LIPUS as non-invasive liquid biopsy technology for UC has been validated in murine models of colitis and translational activities are ongoing for application in human UC patients. A favourable ethics vote and approval from the Italian Ministry of Health has been obtained for the LIPUS Clinical Study, thus leading to study commencement in the following period also in an newly-joined center that will aid recruitment. ImmUniverse created general awareness by producing communication materials such as a flyer, social media designs, an interview clip on dOFM, lay summaries of publications, an animated clip and an FAQ article. Social Media campaigns are ongoing and the audience is increasing. First manuscripts have been published and partners represented the project at conferences.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The ImmUniverse project will bring AD and UC clinical management to a new level through novel, tested and clinic-ready circulating biomarker assays which are expected (a) to improve diagnosis, (b) to inform early in the clinical course on disease severity and progression and (c) to enable treatment response/remission monitoring. Moreover, implementing disruptive non-invasive liquid-biopsy methodologies will provide significant advances; dOFM has the potential to provide a high resolution signature of the intersitual fluid allowing correlation between tissue and blood and support the identification of robust circulating signatures in AD, while LIPUS has the potential to induce tissue-specific cellular and molecular components into the blood allowing the enhancement of circulating signatures, thereby replacing intestinal biospies. This is particularly relevant for UC as currently, biopsy and endoscopic assessment of mucosal healing are the gold standard for the evaluation and diagnosis of inflammatory bowel disease (IBD) progression. Although well tolerated, both endoscopy and biopsies are invasive, thus limiting their use and frequency, and they do not reflect disease dynamics or sensitivity to treatment. Traditional biopsy is limited by the quality and amount of the tissue that can be sampled. Similarly, frequency of biopsy sampling in dermatology is a limiting factor. Therefore, there is a high clinical need for robust signatures of the disease tissue microenvironment from blood and/or non-invasive detection methods that could monitor the real-time dynamics of AD and UC. Liquid biopsy represents an alternative and attractive non-invasive procedure. Therefore, If successful, Immuniverse will significantly enhance our understanding of both diseases, providing tissue-specific biomarker signatures that will transform diagnosis, disease prognosis, and therapy response. These advancements will be crucial for patients, clinicians, and health authorities, offering profound implications for personalized treatment and improved healthcare outcomes.

ImmUniverse Logo