Gut Microbiota-Induced Tregs for Inflammatory-Bowel-Disease (IBD) Immunotherapy (MITI2)

Project Information

MITI 2

Grant agreement ID: 101080445

DOI

10.3030/101080445

EC signature date 28 April 2023

Start date 1 May 2023

End date 30 April 2027

Funded under

• Health

Total cost

€ 6 383 217,00

EU contribution

€ 6 383 217,00

Coordinated by

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 2 - MITI 2 (Gut Microbiota-Induced Tregs for Inflammatory-Bowel-Disease (IBD) Immunotherapy (MITI2))

Reporting period: 2024-11-01 to 2026-04-30

Summary of the context and overall objectives of the project

Inflammatory Bowel Disease (IBD) is a disabling condition that causes many life-altering symptoms including life-threatening complications with a great medical need. The main objective of the MITI2 project is to deliver an immunotherapy product ready to be used in a phase 1 clinical trial to treat IBD patients. The project thus aims at providing a preclinical package including: i) the proof of concept that a cellular immunotherapy using the identified Treg subset represents a clinically suitable treatment for IBD patients and ii) an original gut-explant-based organoid preclinical model, which recapitulates ex vivo the complexity of intestinal physiology. The project is organized in 8 different work packages, all of them closely related one to another.

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

During the second reporting period (RP2), the MITI² project made important progress toward developing new therapies and advanced models for inflammatory bowel diseases (IBD).
Researchers improved the understanding of a special type of immune cell called DP8α regulatory T cells, which may help control intestinal inflammation. They identified promising molecules involved in the interaction between these cells and beneficial gut bacteria and discovered a compound able to strongly enhance the anti-inflammatory activity of these cells.
The project also expanded its collection of patient-derived intestinal organoids, miniature gut models grown from patient tissues. More than 50 organoid lines are now available, including many derived from IBD patients. These models retain characteristics of the disease and provide valuable tools for research.
A major achievement was the successful creation of advanced organoid models combining intestinal cells, immune cells, and nerve cells from the same patient. These innovative models better reproduce the complexity of the human intestine and allow researchers to study how different cell types interact during inflammation.
In parallel, larger and more complex living intestinal models were generated from patient tissues and are being analyzed using advanced imaging technologies to better understand inflammatory processes in real time.
The project also developed a vascularized microfluidic platform that mimics blood vessel networks and can support future integration of organoids under conditions closer to those found in the human body.
Although some activities requiring large numbers of patient samples are still ongoing, important methodological advances were achieved. The project is now well positioned to enter the next phase of testing new therapeutic approaches using these advanced human-based models.

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)

The MITI² project has generated several results that go beyond current knowledge and existing technologies in the field of inflammatory bowel diseases (IBD).
Researchers have gained new insights into a rare population of immune cells called DP8α regulatory T cells, which are believed to play an important role in controlling intestinal inflammation. New molecules involved in their activation have been identified, and a promising compound was found to significantly improve their anti-inflammatory functions. In addition, the project developed methods compatible with future clinical production, bringing these cells closer to potential therapeutic applications.
The project has also created advanced human intestinal models derived directly from patients. Unlike traditional laboratory models, these organoids preserve important characteristics of IBD and therefore provide more realistic tools for studying the disease and testing future treatments.
Another major breakthrough was the development of large patient-derived intestinal organoids grown without animal-derived materials and with a unique “apical-out” structure, allowing direct access to the intestinal surface. This innovative model has not previously been described and could greatly improve the evaluation of new therapies.
MITI² also developed a new vascularized microfluidic platform that reproduces key features of human tissues in a controlled environment. This technology could contribute to more predictive and standardized preclinical testing while reducing reliance on animal models.
Preliminary studies further suggest that interactions between intestinal tissues, immune cells, and nervous system cells may help protect the intestine from inflammation. These findings open new perspectives for understanding disease mechanisms and identifying innovative therapeutic targets.
To ensure the full impact of these results, further research and validation studies will be needed. Standardization of protocols, development of regulatory frameworks, and continued collaboration between academic, clinical, and industrial partners will help facilitate future clinical translation and potential therapeutic applications for patients suffering from IBD.