Microenvironment imposed signatures in tissue and liquid biopsies in immune- mediated diseases

The ultimate goal to be achieved by the consortium is to identify key organ and disease-specific signatures with correlates in body fluids that may predict disease, track progression and/or therapeutic response. These signatures will enable tailored treatment pathways to the disease mechanism and ultimately provide superior therapeutic benefit to patients.

In order to achieve the ambitious overall objective, a set of specific objectives should be addressed by the applicants.

1. Identify and evolve the state-of-the-art novel technologies to interrogate both immune and non-immune cells in target tissues at single cell level to better understand pathways regulating disease and to define tissue/disease-specific signatures, which can be correlated in peripheral blood. The technologies for the identified signature need to be adaptable and of sufficient robustness for use in clinical trial.

2. Evaluate above technologies in existing clinical retrospective cohorts as well as samples from ongoing clinical trials made accessible by both academic and industry partners.

3. Perform a bespoke, enabling clinical study to verify signatures. This will be a non-interventional prospective study, run as a collaborative effort between industry and academic partners.

Biological therapies have provided significant therapeutic benefit to patients with immuno-inflammatory diseases, but many patients fail to respond completely and efficacy is lost in many patients over time. The tissue microenvironment interacts with and influences immune cells to form functional cellular niches that play a role not only in the onset and progression of disease but also in the response to therapy. Inaccessible tissue and invasive biopsy procedures have prevented in-depth interrogation of these microenvironments, resulting in a major gap in our basic understanding of immune cell action mechanisms. Therefore, how they interact with each other and their environment, and how they can be monitored and pharmacologically manipulated to better control disease, remain elusive.

This topic aims to profile tissue-specific microenvironments to improve knowledge of pathophysiology of various immune-mediated diseases (such as inflammatory bowel disease: Crohn’s disease and ulcerative colitis; and skin related diseases e.g. atopic dermatitis, cutaneous lupus, psoriasis) and identify signatures that can be correlated in body fluids (i.e. blood), ‘circulating signatures’, to inform on disease progression and to monitor treatment.

In-depth characterisation of the tissue microenvironment will provide better disease understanding, which represents a significant advance in the assessment of both immune and non-immune markers in relevant diseases. The signatures, but potentially also the relevant (novel) underlying technology, will advance clinical monitoring in both clinical trials and standard patient care. These tools will allow earlier detection of disease progression or identify patients at risk and therefore will allow earlier or more tailored treatment. In clinical trials, these less invasive tools will allow better or earlier detection of treatment response, but may also allow better patient stratification and prediction of treatment response. The proposed non-interventional clinical study will allow verification of signatures and facilitate the implementation of these signatures as decision-making tools for other clinical studies. The less invasive nature of the detection of these signatures is highly attractive, as it will significantly reduce the burden to patients in clinical trials and can complement diagnosis.

The multi-partner, multi-stakeholder and cross-sector approach of this consortium will also allow for a more standardised future adoption of these signatures across industry and pave the way for regulatory approval of improved, clinically relevant tools to monitor disease progression.

Applicants should indicate how their proposal will impact the competitiveness and industrial leadership of Europe by, for example engaging suitable SMEs. In particular, the inclusion of SMEs into the consortium will maximise the opportunity for suitable technology for the identification of disease-specific signatures of the tissue microenvironment to be identified and, more importantly, ultimately implemented in multi-centre clinical trial settings under good laboratory practice (GLP) conditions.