Type 1 Diabetes (T1D) is an autoimmune disease characterized by the infiltration and destruction of insulin producing β-cells of the pancreatic islets by autoreactive T-cells. Treatment with autoantigenic peptide(s) chemically crosslinked with ECDI to splenocytes or other cellular carriers (Ag-ECDI-SP) can prevent and/or reverse murine autoimmune diabetes. Due to the inherit limitations of cellular therapy in a clinical setting including the sourcing and production of Ag-ECDI-SP, here we explore the use of biodegradable poly(lactic-co-glycolic acid) (PLGA) micro-particles as substitutes for splenic donor cells. Treatment with p31-ECDI-PLGA protected against disease in the BDC2.5 adoptive transfer model of T1D. Mice tolerized with p31-ECDI-PLGA mice had reduced levels of total infiltrating BDC2.5 CD4 T cells in the pancreas when compared to mice treated with the non-diabetogenic MOG35-55-ECDI-PLGA control. Additionally, BDC2.5 T cells isolated from the pancreas of p31-ECDI-PLGA treated mice had reduced levels of inflammatory cytokines, such as IFN-gamma, TNF-alpha and IL-17. These data demonstrate the efficacy of an antigen specific therapy to modulate a highly pathogenic autoimmune response using an FDA approved biodegradable PLGA microspeheres. Thus, this carrier system provides a more viable alternative to the cell based approach that can be readily translated in clinical trials.
- Copyright © 2013 by The American Association of Immunologists, Inc.