Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis
Kelly R. Rhodes, Stephany Y. Tzeng, Marcos Iglesias, Dongwoo Lee, Kaitlyn Storm, Sarah Y. Neshat, Derek VanDyke, Shirley M. Lowmaster, Jamie B. Spangler, Giorgio Raimondi, Jordan J. Green
Abstract
Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as “self” rather than “foreign.” As peripheral immune tolerance is primarily mediated by regulatory T cells (T regs ), we developed a therapy to support T reg expansion and activity in vivo. To target, engage, and activate myelin-specific T regs , we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for treatment of autoimmune diseases.