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Ingeniería de la secreción de IL-21 en células T mediante dominios estabilizados por ligandos y susceptibles a
Dong Hyun Kim1, Seo Jin Lee1,2, Taeyoung Ahn1
1Laboratory of Cell & Gene Therapy, Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, 08826, Republic of Korea.
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.
