Allo-THYTECH · Development and implementation in clinical practice of the allogeneic use of thymus-derived regulatory T cells (thyTreg) as a cell therapy to suppress harmful immune responses

Development and implementation in clinical practice of the allogeneic use of thymus-derived regulatory T cells (thyTreg) as a cell therapy to suppress harmful immune responses

The immune system is responsible for defending the body against external threats and preventing the proliferation of tumor cells. However, it can also produce excessive or unwanted responses, leading to inflammatory processes that may cause severe pathologies such as autoimmune diseases, graft rejection, or neurodegenerative disorders. The immunosuppressive drugs commonly used to treat these inflammatory conditions are generally non-specific and can impair all immune responses, including those that protect against infections and cancer. Given these challenges, alternative strategies are being explored to achieve a more balanced immune response without resorting to broad-spectrum immunosuppressive drugs. Among the most promising strategies is cell therapy, which seeks to restore immune balance. Recent scientific studies have shown that the immune system has intrinsic regulatory mechanisms, particularly through regulatory T cells (Tregs), which help control and reduce inappropriate inflammatory responses. This MSCA project focuses on developing an innovative approach to produce Treg cell therapies and overcoming the limitations of current methods to make Treg cell therapy a viable treatment option. The potential outcomes of this project could have significant societal impact by offering new therapeutic options for diseases with a high incidence in the population—approximately 4-6% of the European population is estimated to suffer from some autoimmune disorder. Additionally, this cell therapy could serve as an alternative to immunosuppressive drugs, potentially reducing their severe side effects in patients. Our research is pioneering the use of human Tregs derived from thymic tissue (thyTregs) rather than blood Tregs, which has enabled us to obtain a larger number of higher-quality cells. The thymic tissue used in our research is typically discarded during pediatric cardiac surgeries, allowing us to prepare and cryopreserve hundreds of therapeutic doses of thyTregs. This "ready-to-use" therapy could be administered to patients other than the original donor, enabling allogeneic treatment. The primary objective of this project was to characterize these thyTregs, optimize protocols for their production and cryopreservation, and validate the feasibility and safety of this approach by initiating a first-in-human clinical trial using allogeneic thyTreg therapy. The project has provided valuable insights into the phenotype and functionality of thyTreg cells, demonstrating their potential as an "off-the-shelf" therapy. Our results have also highlighted the advantages and distinctive properties of thyTregs compared to Tregs obtained from other sources.

Data: CORDIS, © European Union