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- W3204247169 abstract "The preferential activation of regulatory T (Treg) cells by interleukin-2 (IL-2), which selectively binds to the trimeric IL-2 receptor (IL-2R) on Treg cells, makes this cytokine a promising therapeutic for the treatment of autoimmune diseases. However, IL-2 has a narrow therapeutic window and a short half-life. Here, we show that the pharmacokinetics and half-life of IL-2 can be substantially improved by orthogonally conjugating the cytokine to poly(ethylene glycol) (PEG) moieties via a copper-free click reaction through the incorporation of azide-bearing amino acids at defined sites. Subcutaneous injection of a PEGylated IL-2 that optimally induced sustained Treg-cell activation and expansion over a wide range of doses through highly selective binding to trimeric IL-2R led to enhanced therapeutic efficacy in mouse models of lupus, collagen-induced arthritis and graft-versus-host disease without compromising the immune defences of the host against viral infection. Site-specific PEGylation could be used more generally to engineer cytokines with improved therapeutic performance for the treatment of autoimmune diseases." @default.
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- W3204247169 date "2021-09-27" @default.
- W3204247169 modified "2023-10-17" @default.
- W3204247169 title "Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells" @default.
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- W3204247169 doi "https://doi.org/10.1038/s41551-021-00797-8" @default.
- W3204247169 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34580438" @default.
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