1062-Tuning STAT Signaling with Trikine Immunotherapeutics

This research introduces Trikines, a novel class of engineered cytokine ligands designed to improve cancer immunotherapy by precisely reconfiguring cellular signaling. Unlike natural cytokines that typically pair two receptor chains, Trikines recruit a third receptor chain to create a three-chain complex, allowing for the simultaneous activation of specific STAT proteins like pSTAT3 and pSTAT5. This "mix-and-match" approach enables scientists to customize immune cell behavior, such as enhancing T cell stemness and survival while reducing the exhaustion often caused by traditional treatments. Preclinical studies demonstrated that these molecules significantly increased antitumor efficacy and survival rates in various cancer models, including melanoma and lung cancer. Notably, Trikines achieved these superior results with a fivefold increase in safety, avoiding the severe systemic toxicities associated with high-dose interleukin therapies. By providing a way to tune immune responses from the cell surface, this technology offers a powerful alternative to complex genetic engineering for developing more effective and tolerable immunotherapeutics.

References:

• Rodriguez G E, Zhao Y, Nishiga Y, et al. Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics[J]. Science, 2026: eadx9954.