Cell therapy strategies for tolerance induction in humans

An important adverse effect that limits the success of gene therapy is the immune response towards genetically modified cells. This response is mainly mediated by a specific subset of cells known as T lymphocytes. Several strategies have been explored to interfere with the anti-transgene immune response, but with limited results. T cell subsets, known as regulatory T (Tr) cells, have been shown to suppress immune responses in several pre-clinical and clinical models. Tr cells represent a promising candidate for the development of novel approaches to suppress immune responses and to prevent the clearance of genetically modified cells. The aim of this proposal is to develop methods to generate antigen-specific Tr cells in vitro using tolerogenic dendritic cells or gene transfer approaches. Results will lead to the development of cellular therapy protocols using trangene-specific Tr cells to prevent clearance of corrected cells after gene therapy.