Engineered Treg Therapy for Multiple Sclerosis (360G-Wellcome-109677_Z_15_Z)

Multiple sclerosis is an inflammatory demyelinating condition of the central nervous system. Although several disease-modifying treatments (DMTs) have been approved to reduce the frequency of clinical relapses, most patients continue to clinically deteriorate under current therapy schedules. Autologous haematopoietic stem cell transplantation can have lasting beneficial effects for patients, but the procedure requires aggressive myelo-ablative conditioning which is associated with substantial toxicity. Neither DMTs nor stem cell transplantation can mediate antigen-specific suppression of the immunopathology of MS. Regulatory T cells (Treg) have the ability to suppress unwanted immune responses of T cells, 8 cells and inflammatory myeloid cells. We have previously shown in a murine model that T cell receptor (TCR) gene transfer is a robust technology to generate antigen-specific Treg. In this project, we will use cell engineering technologies to produce Treg that specifically suppress inflammation in the CNS. The planned preclinical work is expected to provide the basis for clinical trials in patients with MS.