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Immunomodulators

Particulate promotion of tolerance

Nature Reviews Drug Discovery volume 12, pages 22–23 (2013)Cite this article

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The authors had previously demonstrated that covalent coupling of soluble peptides to apoptotic splenic leukocytes efficiently and safely induced antigen-specific immune tolerance following intravenous infusion. However, owing to the potential challenges of scaling up this platform to good manufacturing practice standards, they evaluated the possibility of using nanoparticles — which are widely used as drug delivery vehicles — to deliver the peptides.

First, a myelin proteolipid protein (PLP; a major component of myelin in the central nervous system) peptide was covalently attached to 500 nm-diameter polystyrene nanoparticles. These were then evaluated for their ability to prevent and treat relapsing–remitting experimental autoimmune encephalomyelitis (EAE), an established mouse model of MS. Intravenous injection of the loaded nanoparticles 7 days before induction of EAE protected mice against developing the disease. These nanoparticles also prevented disease initiation when they were given at the first signs of symptoms (which occurred ∼11 days after the induction of EAE). At the cellular level, it was shown that disease attenuation relied on the uptake of nanoparticles by specialized macrophages in the spleen that express the scavenger receptor MARCO and on the modulation of the activities of various T cell populations.

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ORIGINAL RESEARCH PAPER

  1. Getts, D. R. et al. Microparticles bearing encephalitogenic peptides induce T-cell tolerance and ameliorate experimental autoimmune encephalomyelitis. Nature Biotech. 18 Nov 2012 (doi:10.1038/nbt.2434)

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  1. Man Tsuey Tse
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Tse, M. Particulate promotion of tolerance. Nat Rev Drug Discov 12, 22–23 (2013). https://doi.org/10.1038/nrd3916

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