An antigen-encapsulating nanoparticle platform for TH1/17 immune tolerance therapy

Derrick P McCarthy; Jonathan Woon-Teck Yap; Christopher T Harp; W Kelsey Song; Jeane Chen; Ryan M Pearson; Stephen D Miller; Lonnie D Shea

doi:10.1016/j.nano.2016.09.007

An antigen-encapsulating nanoparticle platform for T_H1/17 immune tolerance therapy

Nanomedicine. 2017 Jan;13(1):191-200. doi: 10.1016/j.nano.2016.09.007. Epub 2016 Oct 6.

Authors

Derrick P McCarthy¹, Jonathan Woon-Teck Yap², Christopher T Harp¹, W Kelsey Song³, Jeane Chen³, Ryan M Pearson⁴, Stephen D Miller⁵, Lonnie D Shea⁶

Affiliations

¹ Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
² Department of Biomedical Engineering, Evanston, IL, USA.
³ Department of Chemical and Biological Engineering, Evanston, IL, USA.
⁴ Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
⁵ Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA. Electronic address: s-d-miller@northwestern.edu.
⁶ Department of Biomedical Engineering, Evanston, IL, USA; Department of Chemical and Biological Engineering, Evanston, IL, USA; Chemistry of Life Processes Institute (CLP), Northwestern University, Evanston, IL, USA; The Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA; Department of Obstetrics and Gynecology, Northwestern University, Chicago, IL, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA; Department of Chemical Engineering, University of Michigan, Ann Arbor, MI, USA. Electronic address: ldshea@umich.edu.

Abstract

Tolerogenic nanoparticles (NPs) are rapidly being developed as specific immunotherapies to treat autoimmune disease. However, many NP-based therapies conjugate antigen (Ag) directly to the NP posing safety concerns due to antibody binding or require the co-delivery of immunosuppressants to induce tolerance. Here, we developed Ag encapsulated NPs comprised of poly(lactide-co-glycolide) [PLG(Ag)] and investigated the mechanism of action for Ag-specific tolerance induction in an autoimmune model of T helper type 1/17 dysfunction - relapse-remitting experimental autoimmune encephalomyelitis (R-EAE). PLG(Ag) completely abrogated disease induction in an organ specific manner, where the spleen was dispensable for tolerance induction. PLG(Ag) delivered intravenously distributed to the liver, associated with macrophages, and recruited Ag-specific T cells. Furthermore, programmed death ligand 1 (PD-L1) was increased on Ag presenting cells and PD-1 blockade lessened tolerance induction. The robust promotion of tolerance by PLG(Ag) without co-delivery of immunosuppressive drugs, suggests that these NPs effectively deliver antigen to endogenous tolerogenic pathways.

Keywords: Autoimmune disease; Drug delivery; Immune tolerance; Nanoparticle.

MeSH terms

Animals
Antigens / administration & dosage
Encephalomyelitis, Autoimmune, Experimental / therapy*
Immune Tolerance*
Immunotherapy*
Mice
Nanoparticles / chemistry*
Polyglactin 910 / chemistry
Programmed Cell Death 1 Receptor / immunology
Spleen / immunology
Th1 Cells / immunology*
Th17 Cells / immunology*

Substances

Antigens
Pdcd1 protein, mouse
Programmed Cell Death 1 Receptor
Polyglactin 910

Abstract

MeSH terms

Substances

Grants and funding