Advanced science (Weinheim, Baden-Wurttemberg, Germany)Sep 27, 2026

Adding an Immune Checkpoint Blocker to Lipid Nanoparticles Helps Target Lymph Nodes and Boosts mRNA Vaccine Effectiveness

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Sep 28, 2026

Abstract

Inguinal lymph node targeting was improved by a 6.94-fold increase in mRNA expression using PDL1 inhibitor-incorporated lipid nanoparticles.

Biphenyl-structured amphiphilic PDL1 inhibitors were used to modify lipid nanoparticles.
Higher lymph node targeting was observed, leading to enhanced immune responses.
The incorporation of the fifth component was associated with increased lymph node expansion and immune cell infiltration.
The targeting effect was consistent across different lipid nanoparticle formulations, indicating its potential universality.
These findings suggest that this modified lipid nanoparticle platform may enhance mRNA vaccine efficacy.

Simplified

mRNA-encapsulated lipid nanoparticles (LNPs) have been used to develop vaccines and therapeutics since the COVID-19 pandemic, and clinical studies have demonstrated therapeutic benefits of mRNA vaccines for various cancers. However, current LNP formulations still require functional modifications to tailor them for therapeutic and vaccine applications. Recently, fifth component-incorporated LNPs were developed to finely tune their functionality, including immunogenicity and organ-targeting ability. Here, biphenyl-structured amphiphilic PDL1 inhibitors are employed as a fifth component to modify LNPs. Amphiphilic PDL1 inhibitor-incorporated, ALC0315-based LNPs show higher lymph node targeting, with a 6.94-fold increase in mRNA expression in the inguinal lymph node, thereby improving lymph node expansion and immune cell infiltration and, consequently, inducing greater mRNA vaccine efficacy. Furthermore, a consistent lymph node-targeting effect of the fifth component-containing LNP was observed across studies using the SM102-based LNP formulation, suggesting its universality. In conclusion, this study demonstrates that PDL1 inhibitor-incorporated fifth-component LNP serves as a next-generation platform for mRNA vaccines.

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Adding an Immune Checkpoint Blocker to Lipid Nanoparticles Helps Target Lymph Nodes and Boosts mRNA Vaccine Effectiveness

Abstract

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