Systemic reprogramming of tumour immunity via IL-10-mRNA nanoparticles.

Area of Science:

• Immunology
• Oncology
• Nanotechnology

Background:

• Recombinant interleukin-10 (IL-10) showed preliminary efficacy in early cancer trials but faced challenges with intratumoural accumulation and limited clinical benefit.
• Previous attempts with IL-10 were hindered by insufficient delivery to tumours, restricting its therapeutic potential.

Purpose of the Study:

• To evaluate the efficacy of intravenous IL-10 messenger RNA (mRNA) nanoparticles (IL-10-mRNA@NPs) in preclinical tumour models.
• To assess the potential of IL-10-mRNA@NPs to overcome the limitations of recombinant IL-10 therapy and improve anti-tumour immune responses.

Main Methods:

• Administered intravenous IL-10-mRNA@NPs to preclinical tumour models, including orthotopic hepatocellular carcinoma.
• Assessed tumour immune cell infiltration, dendritic cell maturation, and MHC class I expression.
• Combined IL-10-mRNA@NPs with immune checkpoint blockade in middle-to-late stage tumour models.

Main Results:

• IL-10-mRNA@NPs sustained local IL-10 production, boosting cytotoxic T cell infiltration and dendritic cell activation in immunosuppressive tumours.
• Combination therapy led to complete tumour eradication in 43% of mice and increased median survival sixfold.
• The treatment induced durable anti-tumour immune memory, providing complete protection against tumour re-challenge.

Conclusions:

• Intravenous IL-10-mRNA@NPs represent a promising strategy to enhance anti-tumour immunity and overcome the limitations of recombinant IL-10.
• This nanoparticle-based approach may offer a viable therapeutic option for a wide range of immunosuppressive tumours.
• The combination therapy demonstrated significant efficacy and potential for long-term remission through immune memory.