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Nat Nanotechnol. 2016 Oct;11(10):890-899. doi: 10.1038/nnano.2016.135. Epub 2016 Aug 1.

Improving the efficacy and safety of biologic drugs with tolerogenic nanoparticles.

Author information

1
Selecta Biosciences Inc., 480 Arsenal Street, Watertown, Massachusetts 02472, USA.

Abstract

The development of antidrug antibodies (ADAs) is a common cause for the failure of biotherapeutic treatments and adverse hypersensitivity reactions. Here we demonstrate that poly(lactic-co-glycolic acid) (PLGA) nanoparticles carrying rapamycin, but not free rapamycin, are capable of inducing durable immunological tolerance to co-administered proteins that is characterized by the induction of tolerogenic dendritic cells, an increase in regulatory T cells, a reduction in B cell activation and germinal centre formation, and the inhibition of antigen-specific hypersensitivity reactions. Intravenous co-administration of tolerogenic nanoparticles with pegylated uricase inhibited the formation of ADAs in mice and non-human primates and normalized serum uric acid levels in uricase-deficient mice. Similarly, the subcutaneous co-administration of nanoparticles with adalimumab resulted in the durable inhibition of ADAs, leading to normalized pharmacokinetics of the anti-TNFα antibody and protection against arthritis in TNFα transgenic mice. Adjunct therapy with tolerogenic nanoparticles represents a novel and broadly applicable approach to prevent the formation of ADAs against biologic therapies.

PMID:
27479756
DOI:
10.1038/nnano.2016.135
[Indexed for MEDLINE]

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