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

Cell therapy based on regulatory T cells (Treg) transfer has acquired great interest for the treatment of autoimmune diseases, graft rejection or graft versus host disease (GVHD). Until now, this therapy has not rendered definitive clinical results in humans mainly due to the low number and limited quality of differentiated Treg purified from adult peripheral blood. To overcome these limitations, the host group has developed a new technology to produce massive amounts of GMP Treg derived from the thymic tissue (thyTreg), which are being employed in a clinical trial as an autologous cell therapy in transplanted children. However, the massive amount of thyTreg obtained from each thymus make possible to produce hundreds of doses that could be also employed allogenically to treat a range of immune diseases and patients. My experience and acquired skills in immunology will provide the host with the adequate knowledge to develop the allogenic use of thyTreg. The goal of my research will be to investigate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible its "off-the-self" use, and secondly to initiate a clinical trial to evaluate the safety/feasibility of a therapy with allogenic thyTreg in patients with GVHD. The project will establish the basis for the development of allogenic thyTreg cell therapies to suppress the harmful immune response underlying autoimmune diseases, transplant rejection, GvHD, and cytokine release syndrome associated with CAR-T therapy or clinical progress in COVID-19 patients. This innovative project will reinforce my expertise in immune disorders, gaining experience in translational research from the pre-clinical stages to the development of clinical trials and transfer of technology. Being part of this host institution participating in leading projects and international partnerships provides the ideal environment to complete my training and to develop my leadership abilities to become an independent researcher.