Skip to main content

An antigen-encapsulating nanoparticle platform for T1/17 immune tolerance therapy.

Citation
McCarthy, D. P., et al. “An Antigen-Encapsulating Nanoparticle Platform For T1/17 Immune Tolerance Therapy.”. Nanomedicine : Nanotechnology, Biology, And Medicine, pp. 191-200.
Center University of Michigan
Author Derrick P McCarthy, Jonathan Woon-Teck Yap, Christopher T Harp, Kelsey Song, Jeane Chen, Ryan M Pearson, Stephen D Miller, Lonnie D Shea
Keywords autoimmune disease, drug delivery, Immune tolerance, nanoparticle
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.

Year of Publication
2017
Journal
Nanomedicine : nanotechnology, biology, and medicine
Volume
13
Issue
1
Number of Pages
191-200
Date Published
12/2017
ISSN Number
1549-9642
DOI
10.1016/j.nano.2016.09.007
Alternate Journal
Nanomedicine
PMID
27720992
PMCID
PMC5237397
Download citation