Journal of nanobiotechnologySep 2, 2025

Spleen-focused NeoPol-mL242 mRNA vaccine triggers strong T-cell responses in liver cancer models

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

A spleen-targeted NeoPol-mL242 showed anti-tumor immune activity in a model.

Evidence

This was a preclinical formulation and cancer-vaccine experiment using an ionizable lipid nanoparticle platform and an HCC model.

Caveat

The evidence is limited to model-system testing, so human efficacy, delivery behavior, and safety remain unproven.

Simplified

Personalized neoantigen peptide vaccines have shown remarkable anti-tumor activity across diverse cancer types. With the rapid advancement of messenger RNA (mRNA) delivery technologies during the coronavirus disease of 2019 (COVID-19) pandemic, mRNA-based cancer vaccines have emerged as a promising therapeutic approach because of their scalable production, safety, and capacity to elicit potent immune responses. However, the predominant distribution of mRNA delivery systems in the liver may lead to hepatic damage and restrict therapeutic accessibility. In this study, we designed a novel ionizable lipid library to shift the delivery to the spleen. By incorporating an additional anionic lipid, we identified an optimized vaccine formulation, which exhibited efficient uptake by dendritic cells (DCs). Notably, this formulation achieved spleen-selective delivery without requiring targeting ligand modifications, thereby minimizing cytotoxicity risks. Furthermore, the spleen-targeted L242-20Lipo nanoparticle was employed to facilitate the efficient delivery of personalized neoantigen mRNA vaccines. Evaluation in a (HCC) model demonstrated that the NeoPol-mL242 elicited potent anti-tumor immunity while maintaining an excellent safety profile. These results highlight NeoPol-mL242 as a promising candidate for application in cancer immunotherapy.

Key numbers

~ 90%

Tumor Burden Reduction

Compared to control groups receiving no treatment.

3.5%

CD8 T-cell Infiltration Increase

CD8 T-cell activation in treated versus control groups.

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Spleen-focused NeoPol-mL242 mRNA vaccine triggers strong T-cell responses in liver cancer models

Abstract

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