Periodic Reporting for period 3 - ImmUniverse (Better control and treatment of immune-mediated diseases by exploring the universe of microenvironment imposed tissue signatures and their correlates in liquid biopsies)
Periodo di rendicontazione: 2022-01-01 al 2022-12-31
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 of 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 investigate 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.
The consortium has further progressed in building up the overall infrastructure to enable integrative data analysis, notably through the implementation of a computational platform, populated with several data analysis, visualization and prediction tools.
Regarding retrospective studies, six clinical centers have obtained ethical approval and made their samples available to the consortium. These include several biomaterials originating from both Ulcerative Colitis (UC) and Atopic Dermatitis (AD) patients and different types of –omics datasets. Analytical protocols for different types of samples and biomolecules have been developed and validated and first analyses employing retrospective samples and datasets have been performed and are currently being integrated with clinical data.
Eight clinical centers have obtained ethical approval for prospective clinical studies and recruitment is currently ongoing or due to start in early 2023. As of end 2022, 87 and 90 patients have been enrolled for UC and for AD, respectively. Due to COVID-related issues, some centers are expected to underrecruit and mitigation plans are being developed.
dOFM has been set up as non-invasive liquid biopsy technology for AD in two clinical centers sites. Patient recruitment, as well as the analysis of the first samples are in progress. All preclinical studies for LIPUS application as disruptive liquid biopsy for UC have been completed and optimal conditions and protocol for clinical translation have been defined. Study protocol has been submitted for ethical approval at the end of 2022.
ImmUniverse started to create general awareness by producing communication materials such as an animated clip and an FAQ article, both can be found on the website. Social Media campaigns are ongoing. A position paper was published by Frontiers in Immunology (https://www.frontiersin.org/articles/10.3389/fimmu.2022.1002629/full).
Regarding retrospective studies, six clinical centers have obtained ethical approval and made their samples available to the consortium. These include several biomaterials originating from both Ulcerative Colitis (UC) and Atopic Dermatitis (AD) patients and different types of –omics datasets. Analytical protocols for different types of samples and biomolecules have been developed and validated and first analyses employing retrospective samples and datasets have been performed and are currently being integrated with clinical data.
Eight clinical centers have obtained ethical approval for prospective clinical studies and recruitment is currently ongoing or due to start in early 2023. As of end 2022, 87 and 90 patients have been enrolled for UC and for AD, respectively. Due to COVID-related issues, some centers are expected to underrecruit and mitigation plans are being developed.
dOFM has been set up as non-invasive liquid biopsy technology for AD in two clinical centers sites. Patient recruitment, as well as the analysis of the first samples are in progress. All preclinical studies for LIPUS application as disruptive liquid biopsy for UC have been completed and optimal conditions and protocol for clinical translation have been defined. Study protocol has been submitted for ethical approval at the end of 2022.
ImmUniverse started to create general awareness by producing communication materials such as an animated clip and an FAQ article, both can be found on the website. Social Media campaigns are ongoing. A position paper was published by Frontiers in Immunology (https://www.frontiersin.org/articles/10.3389/fimmu.2022.1002629/full).
The ImmUniverse project will bring Atopic Dermatitis (AD) and Ulcerative Colitis (UC) clinical management to a new level through novel, validated 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 aid in identification of robust circulating signatures in AD, while LIPUS has the potential to induce tissue specific cellular and molecular components into the blood allowing induction of circulating signatures, thereby replacing intestinal biospies. This is particularly relevent for UC as currently, biopsy and endoscopic assessment of mucosal healing are the gold standard for the evaluation of diagnosis and 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 the 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. The liquid biopsy represents an alternative and attractive non-invasive procedure. If successful, Immuniverse will provide tissue-specific biomarker signatures that will significantly advance diagnosis, disease prognosis and therapy response, which will be of extreme importance to patients, clinicians and health authorities.