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Tetravalent IL-10R nanobody agonist achieves myeloid-selective immunosuppression through TYK2 dependence
In brief
A Gilead Sciences team publishing in Nature designed a tetravalent nanobody IL-10R agonist that achieves myeloid-selective immunosuppression through TYK2 dependence. In humanized mice the molecule attenuated LPS challenge, delayed-type hypersensitivity and colitis; in non-human primates it showed IgG-like long half-life pharmacokinetics with receptor occupancy maintained for 30 days, no T-cell activation and no hematologic toxicity.
Why it matters
The tetravalent configuration makes signaling nearly fully TYK2-dependent, offering a transferable design to separate therapeutic from toxic cytokine effects.
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