Tolerogenic Vaccination Using Gene-Silenced Dendritic Cells for Autoimmune Arthritis
Rheumatoid arthritis (RA) is a progressive autoimmune disease characterized by chronic inflammation of synovial tissue, pannus formation, cartilage destruction and bone erosion. Clinically, RA is believed to affect between 0.5 and 1.0% of the adult population worldwide, with a higher predilection for females. Although currently used TNF-?-targeting therapies have shown clinical promise, these agents are restricted only to severe arthritis and are associated with side effects such as increased incidence of autoantibody formation and reactivation of tuberculosis. Therapies based on antigen-specific tolerance for arthritis that do not require systemic immune suppression are yet to be devised. We have recently developed several strategies for generating tolerogenic dendritic cells (Tol-DC) that are capable of inducing antigen-specific immune modulation in animal models that mirror transplantation and RA. These strategies for generating Tol-DC include immune suppressants, gene transfection and gene silencing
Unlike conventional dendritic cells (DC) that program T cells to attack foreign antigens (such as a microbe or an allogeneic transplant), Tol-DC are capable of suppressing immune responses in an antigen specific fashion. ToleroTech has been developing new RNAi-based therapy to prevent and treat arthritis using siRNA or siRNA-silenced Tol-DC. These new siRNA treatments establish platforms for novel therapeutic interventions in arthritis patients.
