A tolerogenic dendritic cell–based therapy targeting heat shock protein–specific regulatory T cells in rheumatoid arthritis

Abstract

Current treatments for RA are merely symptomatic, cause unwanted side effects (steroids), involve monoclonal antibodies that inactivate the immune system, and produce serious side effects and at great cost. We have developed a therapeutic peptide vaccine based on the discovery that HSP function as natural targets that induce the immune system to regulate the inflammatory response. HSP70-derived peptide B29 is now being tested in RA patients by loading the peptide into autologous tolerogenic dendritic cells (TolDCB29) and by injecting these tolDCs into inguinal lymph nodes. The herewith induced immune response is targeted toward the sites of inflammation where HSP are naturally expressed, avoiding the unwanted side effects of general immune suppression. Our approach builds on earlier trials in which tolDCs were reported as safe to administer using various administration routes. The exact specificity of the HSP70 B29 peptide-induced tolerance enables the precise monitoring of the induced immunological effect.