articleScienceFeb 19, 2026GREEN OA

Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics

GEGrayson E. RodriguezYZYang ZhaoYNYoko NishigaFPFrank PeprahJSJiao Shen

Stanford University · Massachusetts General Hospital · +13 more institutions

PubMed
Indexed incrossrefpubmed

Abstract

Cytokines dimerize two receptor chains to activate Janus kinases and signal transducer and activator of transcription (STAT) transcription factors that regulate immune cells, but they have therapeutic liabilities. We engineered “Trikines” to compel cis formation of three-chain cytokine receptor complexes at the cell surface that induce bespoke STAT transcriptional signaling programs. Trikines coactivated phosphorylation of STAT5 (pSTAT5) and pSTAT3 signatures distinct from natural cytokines by assembling trimeric combinations of interleukin-2 (IL-2), IL-10, and IL-21 receptors. In preclinical models, an IL-2–based Trikine restrained terminal differentiation of T cells, promoted stemness, and enhanced…

Citation impact

5
total citations
FWCI
58.90
Percentile
100%
References
67
Too recent for citation history.

Authors

37

Topics & keywords

Topics
Keywords
  • stat
  • Immune system
  • JAK-STAT signaling pathway
  • Cytokine
  • Cell
  • Signal transduction
  • Janus kinase
  • Transcription factor
No related works found for this paper.

Funding