Combinatorial, microparticle-based delivery of immune modulators reprograms dendritic cell phenotype and promotes remission of collagen-induced arthritis in mice

Statement of Purpose: Rheumatoid arthritis (RA) is a chronic, disabling autoimmune condition afflicting about 0.3 – 1% of the world’s adult population[1]. One potential avenue for treatment of RA is the development of RA-specific tolerogenic dendritic cells (tDCs). Tolerogenic DCs (tDCs) are an attractive solution for treatment of RA in that they target the immune cascade responsible for RA, rather than addressing the symptoms as with most convention therapies. Previously, it has been demonstrated that exogenously-treated tDCs can limit autoimmunity in a RA murine model[2]. However, ex-vivo stability and manufacturing cost inhibit the widespread use of exogenously-treated tDCs in autoimmune treatments. In an effort to circumvent drawbacks with exogenously-derived tDC therapy, an “anti-vaccine" (Avac) delivering tolerogenic factors via poly (lactic-co-glycolic acid) (PLGA) microparticles (MPs) that passively target DCs has been explored as a potential system for autoimmune disease treatment[3]. Our working hypothesis is that this Avac will modulate DC phenotype in vivo, thereby modulate downstream T and B cell responses, ultimately suppressing autoimmunity in a collagen-induced arthritis (CIA) murine model.