ArticleScientific reports2025
Engineering IL-21 secretion in T cells using druggable ligand-responsive stabilized domains.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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6 authors.
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Abstract
Cytokine-based immunotherapies face challenges due to systemic toxicity and uncontrolled cytokine release. To enable precise control, we developed a druggable ligand-dependent IL-21 secretion system using destabilization domains (DDs). ER50 and DHFR facilitated ligand-responsive IL-21 secretion, with ER50 providing the most sustained regulation. Structural analysis revealed that N-terminal fusion improved IL-21 receptor binding, while C-terminal fusion weakened interactions. In primary T cells, IL-21 secretion promoted T stem-like (Tscm) cell differentiation, enhancing persistence for adoptive cell therapy. This system enables reversible, tunable cytokine control, offering a safer and more flexible approach for engineered T cell therapies.
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