Stable IL-2 Nano-Assembly for Improved Anti-Tumor Effect

Interleukin 2 (IL-2) is the first approved immune therapeutic drug to treat cancer, however various off-target effects and intolerable dose-related toxicities induced by high-dose intravenous infusion regimens result in a large proportion of patients require dose reduction, preventing the widespread adoption of this treatment. To address these issues, a novel IL-2 nano-assembly formulation (nano-IL-2) is developed using distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethylene glycol)-2000] (PEG2000-DSPE), which is durably stable due to the high binding affinity (10-8 m level) of two components and hardly induces vascular leak or inflamed injury at the injection site. Besides, nano-IL-2 exerts excellent solubility, lymph-targeting property, prolonged and stable serum IL-2 concentration ranges, and much lower toxicities compared to commercial formulation. Monotherapy of nano-IL-2 shows optimal capability to control the growth of murine melanoma and colon cancer. Collectively, the present study provides a novel design strategy for lymph-targeting IL-2 formulation which is more suitable for subcutaneous administration with higher safety concern. The present study has demonstrated that pharmacokinetic advantages of nano-interleukin 2 (IL-2) formulation over commercial formulation, including increased stability, comparable bioavailability, extended serum retention time, and better anti-tumor efficacy. These properties allow the potential clinical use of nano-IL-2 to decrease the dosing frequency of IL-2 and avoid immune-related adversaries in cancer patients.image