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Interleukin 2 (IL2) selectively binds to regulatory T cells (Treg) trimer on IL2 receptor (of IL-2R) , preferentially activate Treg cells, IL2 become promising therapeutic self- immune diseases Cytokines
.
However, IL-2 has a narrow therapeutic window and short half-life
Interleukin 2 (IL2) selectively binds to regulatory T cells (Treg) trimer on IL2 receptor (of IL-2R) , preferentially activate Treg cells, IL2 become promising therapeutic self- immune diseases Cytokines
In this study, Professor Zhang Xu from Xiehe Hospital and his cooperating team incorporated azide-containing amino acids at designated sites through a copper-free click reaction, and orthogonally combined cytokines with polyethylene glycol ( PEG ) to obtain the drug.
pharmacokinetic half-life and greatly enhanced IL-2 (as shown above), especially in the Tyr31 and Thr51 sites are 20 kDa PEG of IL-2 preferentially binds IL-2α subunit instead of β -subunit, As a result, Treg cells are continuously activated and the degree of activation of CD8+ T cells is low
.
Subcutaneous injection of different doses of PEGylated IL-2 induces continuous activation and expansion of Treg cells by highly selective binding to the trimeric IL-2R , which can enhance lupus, collagen-induced arthritis and graft-versus-host mice The disease treatment effect of the model does not damage the host 's immune defense against viral infections .
In this study, Professor Zhang Xu from Xiehe Hospital and his cooperating team incorporated azide-containing amino acids at designated sites through a copper-free click reaction, and orthogonally combined cytokines with polyethylene glycol ( PEG ) to obtain the drug.
in conclusion:
in conclusion:More general design of site-specific cytokine PEGylation can improve its therapeutic performance for the treatment of autoimmune diseases
.
.
Source:
Zhang B, Sun J, Wang Y, Ji D, Yuan Y, Li S, Sun Y, Hou Y, Li P, Zhao L, Yu F, Ma W, Cheng B, Wu L, Hu J, Wang M, Song W , Li X, Li H, Fei Y, Chen H, Zhang L, Tsokos GC, Zhou D, Zhang X.
Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells.
Zhang B, Sun J, Wang Y, Ji D, Yuan Y, Li S, Sun Y, Hou Y, Li P, Zhao L, Yu F, Ma W, Cheng B, Wu L, Hu J, Wang M, Song W , Li X, Li H, Fei Y, Chen H, Zhang L, Tsokos GC, Zhou D, Zhang X.
Site-specific PEGylation of interleukin-2 enhances immunosuppression via the sustained activation of regulatory T cells.
Nat Biomed Eng.
2021 Sep 27.
doi: 10.
1038/s41551-021-00797-8.
Epub ahead of print.
PMID: 34580438.
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