Messenger RNA delivery of a specially designed IL-2 boosts and extends anti-tumor T cell response by targeting two immune receptors

Alb-IL-2var RNA-LNP demonstrates a favorable pharmacokinetic profile and is tolerated at biologically active doses in immunocompetent mice and cynomolgus monkeys.

• IL-2var is engineered to selectively stimulate CD8⁺ T cells over regulatory T (T_reg) cells by reducing binding to IL-2Rα (CD25) and enhancing binding to IL-2Rβ (CD122).
• The variant is delivered as an mRNA encapsulated in a lipid nanoparticle, allowing for sustained exposure through hepatic production.
• In vitro studies show selective enhancement of CD8⁺ T cell responses over T_reg cells in human blood samples.
• In vivo studies confirm similar selective responses in mice and cynomolgus monkeys.
• Alb-IL-2var RNA-LNP stimulates expansion of tumor-infiltrating and circulating tumor antigen-specific CD8⁺ T cells when combined with an mRNA cancer vaccine.
• The combination enhances the efficacy of radiotherapy and checkpoint inhibitors in advanced and cold tumor models.

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