Nanoimmunotherapy for chronic immune-mediated diseases

ABSTRACT
Current pharmaceutical agents that are used for the treatment of immune-mediated inflammatory
conditions including autoimmune diseases generally do not lead to remission and frequently carry toxic
side effects. Here we propose a strategy that can harness the capacity of the immune system to induce
immunoregulatory response that can suppress immune hyperactivity and chronic inflammation in vivo.
The product that we propose consists of nanoparticles (NPs) targeted to immunoregulatory cells for
their expansion and functional activity in vitro and in vivo. Our approach to generate and expand
functional immunoregulatory cells that become impaired in autoimmune diseases should contribute to
restoring immune homeostasis and improve disease outcomes. This approach is especially designed
to treat systemic lupus erythematosus. The proof-of-concept for this Phase 1 studies will be to show
that our cell-targeted NPs can markedly expand ex vivo both CD4+ and CD8+ Tregs, and TGF-ß
producing NK regulatory cells that we recently described. Complementary experiments in humanized
mice will address the in vivo functional efficacy of those NP-induced immunoregulatory cells in
suppressing effector immune responses in vivo, including in an animal model of human lupus. By
demonstrating that NP-expanded human immunoregulatory cells are functional in vivo in humanized
mice, we propose a new nanoimmunotherapeutic approach to restore immune regulation and induce
remission in autoimmune disease. Importantly, this in vivo cell-targeted strategy has the potential to
overcome the undesired side effects of the broadly non-specific, anti-inflammatory and
immunosuppressive drugs presently used to treat autoimmune diseases.PROJECT NARRATIVE (Relevance to Public Health)
According to the National Institutes of Health, up to 23.5 million Americans (more than 7% of the population)
suffer from an autoimmune disease - and the prevalence is rising. Autoimmune diseases can cause severe
disability due to the lack of a cure, and the drugs used to suppress inflammation focus on delaying disease
progression to reduce mortality but often have serious adverse side effects. This proposal describes a new
strategy that uses nanoparticles to deliver therapeutic agents in minute amounts (thus minimizing toxicity) for
the expansion of immune cells that effectively suppress inflammation and rebalance the autoimmune
abnormalities in vivo.