Scholarlink

<p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engineering IL-21 secretion in T cells using druggable ligand-responsive stabilized domains

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月27日

查看全文
  • Dong Hyun Kim,
  • Seo Jin Lee,
  • Taeyoung Ahn,
  • Hyung-Young Kim,
  • Kyungsu Kim,
  • Hyungseok Seo

摘要

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.