Riley Allen1 Amir Bolandparvaz1 Jamal Lewis1

1, University of California, Davis, Davis, California, United States

Introduction: Current paradigms for the treatment of autoimmune diseases (e.g. rheumatoid arthritis [RA]) are woefully inadequate, often missing the mark on desired physiological responses and not targeting the root cause of the disease. Predictably, novel approaches to re-establish immune homeostasis in patients afflicted by autoimmune conditions are now under intense investigation. Notably, we are developing an array of multifunctional, biomaterial-based ‘anti-vaccines’ that can be easily administered to remediate some of the prevalent autoimmune diseases. This talk will focus on different particulate systems currently under development in my lab, which attempt to control critical cellular and humoral mediators that engender conditions such as type 1 diabetes, RA, and autoimmune autism.

Dual microparticle anti-vaccine for conditioning dendritic cells in vivo: The underlying cause of RA is dendritic cell (DC) activation of antigen-specific T cell subsets in the joints, which drive inflammatory responses to the synovial membrane that are typically characterized by inflammatory cell infiltration and over production of pro-inflammatory cytokines by monocytes, macrophages and synovial fibroblasts. The Lewis Lab at UC, Davis is developing a novel, dual microparticle system for in vivo co-delivery of pro-tolerance factors and autoantigens, targeted to DCs. Exogenous conditioning of DCs with certain immuno-modulatory agents has been shown to induce pro-tolerance DC phenotypes that ameliorate RA. We are attempting to build on those successes by using materials to circumvent ex-vivo conditioning, which has been shown to be disadvantageous to full translation into the clinic. Further, we are interested in deciphering the immune effects of synthetic biomaterials on critical immune cells and delineate the properties of biomaterials that influence immune cell polarity.

Biomagnetic Traps for Treatment of Autoimmune Autism: Contemporary molecular biology techniques have helped to shed light on one key trigger of autism – the transfer of maternal autoantibodies against critical proteins in the developing fetal brain during pregnancy, which results in the development of approx. 23% of all autism cases. Further, researchers have pinpointed the specific antigenic determinants recognized by these autism-causing maternal autoantibodies. We seek developing a therapeutic measure for autoimmune autism based on this new knowledge. The immunomodulatory biomaterials lab at UC Davis is currently engineering `biomagnetic traps' – iron oxide-based nanoparticles (NPs) that are surface-conjugated with cognate peptides (epitopes), for the removal of circulating, ASD-causing maternal autoantibodies. Our long-term goal is to develop a modular, nanoparticle platform for autoantibody sequestration and treatment of maternal autoantibody-related (MAR) ASD.