Towards a "negative" cellular vaccine for the treatment of multiple sclerosis: counter-acting epitope spreading for long-lasting tolerance induction using mRNA-electroporated tolerogenic dendritic cells.

Multiple sclerosis (MS) is an inflammatory disease that affects 1 out of 1000 people in Europe. MS is mediated by an autoimmune response to components or antigens of the insulating cover of the nerves of the central nervous system, i.e. myelin antigens, which are no longer recognised as being 'self'. This causes progressive destruction of the nerves of the brain and spinal cord, presenting as a wide range of motor and sensory disturbances. On the basis of our recent research, we hypothesise that specific cells of theimmune system, i.e. dendritic cells (DC), regulate the immune response by inducing immunity or tolerance towards specific antigens. Therefore these DC might be used to suppress abnormal immune responses in autoimmune diseases such as MS. The final aim will be to induce tolerance to myelin antigens by administering DC to MS patients, which might lead to a change in the natural course of the disease. Several techniques exist for the loading of DC with specific antigens, which makes them tolerance inducing for specific autoimmune responses rather than being overall immunosuppressive. We will compare two of these techniques, in combination with a dose escalation vaccine study in MS patients in order to ensure patient safety when administrating a vaccine with tolerance-inducing DC. Patients will be divided in two groups, comparing both antigen-loading strategies by evaluating adverse events, relapse-free interval and immunological response after vaccination.

Keywords:TOLERANCE, CELL THERAPY, MULTIPLE SCLEROSIS, DENDRITIC CELLS

Disciplines:Immunology, Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing