Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions

Project Information

3TR

Grant agreement ID: 831434

DOI

10.3030/831434

EC signature date 22 August 2019

Start date 1 September 2019

End date 31 August 2028

Funded under

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

Total cost

€ 87 721 177,75

EU contribution

€ 40 273 191,50

Coordinated by

FUNDACION PUBLICA ANDALUZA PROGRESO Y SALUD M.P.
Spain

Periodic Reporting for period 4 - 3TR (Identification of the Molecular Mechanisms of non-response to Treatments, Relapses and Remission in Autoimmune, Inflammatory, and Allergic Conditions)

Reporting period: 2024-03-01 to 2025-08-31

Summary of the context and overall objectives of the project

Patients from several immune-mediated diseases experience continued trial-and-error testing of new drugs without adequate selection based on personalized molecular patterns of disease. In consequence, the patients suffer from not having an adequate response to the therapy they are given, causing perpetuation of tissue damage or even death. The main objective of 3TR is therefore to define the molecular mechanisms behind this therapeutic unresponsiveness in patients from 7 different immune-mediated diseases, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, asthma, chronic obstructive pulmonary disease and inflammatory bowel disease - diseases that affect important portions of the European population. As secondary objectives, 3TR has as the goal to define new therapeutic targets through the molecular stratification of patients according to their tissue molecular structure and to define biomarkers that can be used in the future to design personalized therapies. Finally, 3TR will also identify the mechanisms behind the appearance of the biomarkers using novel methodologies such as tissue organoids. The results will have a major impact in the society, as it will lead to a more personalized approach towards therapy and reduce severe tissue damage and invalidation.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

By the end of the fourth reporting period, 3TR has accomplished 100% recruitment of the patients in most of the prospective observational studies. The operations management team, created to ensure the flow of the pipeline from sample to data continuous its work. In this flow, a large volume of patient samples have been sequenced and genotyped. Working groups for the analyses of single cell data, in the form of scRNASeq, mass cytometry or imaging have set up their tools and necessary materials to begin receiving tissue samples. In addition, data from industry clinical trials have been uploaded and results are presented. Samples from prior existing studies and trials have been included in the pipelines and are also sequenced. Across disease analysis plans have been agreed and analyses have started. The work has resulted in several publications which are accessible via the 3TR website (www.3tr-imi.eu).

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

We expect to identify the molecular patterns and the mechanisms behind the unresponsiveness to the therapies given to patients of 7 different immune-mediated diseases. We will also identify biomarkers for severity and activity for each of them but also biomarkers that may allow their use across diseases and the mechanisms that may overlap between them. In addition, we will define the mechanisms of action of some of the drugs and their activity in certain patients and not others through in vitro organoid studies that will be feasible to do in the prospective studies, particularly in the case of the IBDs.
These studies will help to improve the approaches to personalized medicine by arming frontline healthcare providers with more information to place patients on the right treatment at the right time. This will reduce the severity and damage of the disease by choosing the best treatment option right from the start. In consequence, the results of 3TR will reduce the costs of pharmacotherapy and the burden of a suboptimal treatment by helping to avoid them.
Finally, the results of this project will offer economic opportunities to European companies to exploit those results e.g. for the development of biomarker test kits. 3TR will therefore have an important social and economic impact in Europe.

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