Clinical therapies for autoimmune diseases, such as multiple sclerosis (MS), rely on broad immunosuppression to halt the attack of “self.” In contrast, experimental therapies for MS aim to re-program how the body responds specifically to myelin – the self-molecule attacked – without compromising healthy immune function. Recent studies reveal inflammatory pathways (e.g., TLRs) are overactive in mouse models and human disease. Thus, we hypothesized co-delivery of a regulatory TLR9 ligand, GpG, with myelin peptide could blunt pro-inflammatory signaling, promoting myelin-specific T cells that exhibit regulatory functions and control disease. We employed electrostatic interactions to form immune polyelectrolyte multilayers, “iPEMs” (Fig. 1A). These structures mimic attractive features of biomaterials, including co-localization of cargos with tunable absolute (Fig. 1B) and relative (Fig. 1C) loading. However, iPEMs are composed entirely of immune cues, eliminating all synthetic polymers or carriers, components that can exhibit intrinsic inflammatory properties that could exacerbate disease. To test tolerogenic potential, mice were induced with a common model of MS (EAE); treatment at peak disease with iPEMs dramatically reduced mean clinical score, functionally reversing paralysis (Fig. 1D). To explore translational potential, iPEMs were incubated with peripheral blood mononuclear cells from human MS patients. iPEMs containing GpG reduced inflammation (i.e., cytokine secretion) compared with control formulations, supporting iPEMs as a carrier-free platform to combat autoimmunity.

Engineered polyelectrolyte multilayers to promote immune tolerance

253rd National Meeting (2017)

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