Abstract
AbstractInterleukin 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.
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