Interleukin-12 is one of the most powerful cytokines in cancer immunotherapy, capable of activating CD8⁺ T cells and NK cells and reshaping the tumor microenvironment. Yet for decades, its clinical use has been constrained by systemic toxicity and short in-vivo half-life when delivered as recombinant protein.

In the cmRNA1210 program from Suzhou CureMed and Purecodon, circRNA encoding human IL-12 is delivered intratumorally. One striking figure compares protein expression over time: circRNA-IL-12 generates higher and much more sustained local IL-12 levels than linear mRNA, maintaining expression for days instead of rapidly decaying. This durability is exactly what is needed to continuously program the immune microenvironment rather than giving a transient cytokine pulse.

A second key figure shows tumor growth curves in multiple solid tumor models (including MC38 and B16F10). circRNA-IL-12 produces dose-dependent tumor regression, and when combined with anti-PD-1, the effect is clearly synergistic — tumors shrink more and survival is significantly prolonged compared with either monotherapy.

These data visually demonstrate a core principle in immunotherapy: efficacy is not only about which cytokine you use, but where, how long, and at what concentration it is expressed. CircRNA shifts IL-12 from a systemically toxic molecule to a locally persistent immune-reprogramming signal.

With China NMPA IND already approved and U.S. IND submitted, this platform is now moving from preclinical proof-of-concept to global clinical translation — opening a new chapter for cytokine-based therapy in solid tumors.