Research ArticleImmunology

Engineered IL-10 variants elicit potent immunomodulatory effects at low ligand doses

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Science Signaling  15 Sep 2020:
Vol. 13, Issue 649, eabc0653
DOI: 10.1126/scisignal.abc0653

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Building a better IL-10

The cytokine IL-10 suppresses inflammation and enhances the cytolytic activity of T cells. However, exogenously administered IL-10 has not been therapeutically successful, likely because of low bioavailability in the target tissue. IL-10 binds to a heterodimeric receptor composed of IL-10Rα subunits (to which it binds with high affinity) and IL-10Rβ subunits (to which it binds with lower affinity). Gorby et al. engineered an IL-10 variant with higher affinity for IL-10Rβ than that of wild-type IL-10. At low concentrations, this variant more potently triggered changes in gene expression in monocytes and CD8+ T cells that would be expected to suppress inflammation. CAR T cells cultured with this variant were more effective at killing acute myeloid leukemic cells. Thus, IL-10 therapy may become clinically feasible using variants with enhanced affinity for IL-10Rβ.

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