An Injectable Cytokine Trap for Local Treatment of Autoimmune Disease

Abstract

Systemic cytokine therapy is limited by toxicity due to activation of unwanted immune cells in off-target tissues. Injectable nanomaterials that interact with the immune system have potential to offer improved pharmacokinetics and cell specificity compared to systemic cytokine therapy by instead capturing and potentiating endogenous cytokine. Here we demonstrate the use of high aspect ratio polycaprolactone nanowires conjugated to cytokine-binding antibodies that assemble into porous matrices when injected into the subcutaneous space. Nanowires are well tolerated in vivo over several weeks, incite minimal foreign body response and resist clearance. Nanowires conjugated with JES6-1, an anti-interleukin-2 (IL-2) antibody, were designed to capture endogenous IL-2 and selectively activate tissue resident regulatory T cells (Tregs). Together these nanowire-antibody matrices were capable of sequestering endogenous IL-2 in the skin and were successful in rebalancing local immune compartments to a more suppressive, Treg-mediated phenotype in both wild type and transgenic murine autoimmune disease models.

Keywords: Autoimmunity; Cytokines; Immunomodulation; Nanomaterials.