New therapies targeting innate immune cytokines have and continue to revolutionalise our capacity to treat autoimmune diseases, like rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Immunotherapies are now revolutionising treatment of certain cancers. However, these treatments are expensive, are generally not curative and may have side effects. Furthermore, no immunotherapies have survived phase 3 trials to reach the market for Type 1 Diabetes (T1D).
In a phase I clinical trial, intradermally-injected autologous DCs exposed to citrullinated peptides and the NF-kB inhibitor, BAY11-7082, reduced circulating effector T cells and increased the ratio of regulatory to effector T cells in RA. However, simpler strategies are desirable for widespread clinical use. We developed antigen-specific liposomal nanoparticle immunotherapy which passively targets and modifies dendritic cells in situ. The liposomes co-encapsulate a disease-specific peptide and an NF-kB inhibitor. Models of inflammatory arthritis and autoimmune diabetes demonstrate antigen-specific suppression of disease development and severity, providing proof-of-concept for translation towards RA and T1D clinical trials. In this talk I will discuss cellular and cytokine-mediated mechanisms involved in the induction of antigen-specific tolerance using liposome immunotherapy.