# Advances in mRNA-Based Melanoma Vaccines: A Narrative Review of Lipid Nanoparticle and Dendritic Cell Delivery Platforms

## TL;DR

mRNA vaccines for melanoma, delivered via lipid nanoparticles or dendritic cells, boost T-cell responses and show early clinical success when combined with immune checkpoint inhibitors.

## Contribution

This review highlights the clinical potential of mRNA-based melanoma vaccines using lipid nanoparticle and dendritic cell delivery systems.

## Key findings

- Personalized mRNA vaccines using lipid nanoparticles enhance neoantigen-specific T-cell responses and improve recurrence-free survival.
- Dendritic cell-based mRNA vaccines show strong immunogenicity when DC maturation is optimized.
- Combining mRNA vaccines with immune checkpoint inhibitors improves clinical outcomes in melanoma.

## Abstract

What are the main findings?
mRNA-based melanoma vaccines delivered through lipid nanoparticles (LNPs) or dendritic cells (DCs) generate strong neoantigen-specific T-cell responses.Personalized mRNA vaccine platforms show early clinical benefit, especially when combined with immune checkpoint inhibitors.

mRNA-based melanoma vaccines delivered through lipid nanoparticles (LNPs) or dendritic cells (DCs) generate strong neoantigen-specific T-cell responses.

Personalized mRNA vaccine platforms show early clinical benefit, especially when combined with immune checkpoint inhibitors.

What are the implications of the main findings?
Optimizing delivery systems and neoantigen selection may further enhance the therapeutic impact of mRNA melanoma vaccines.Hybrid and personalized vaccine strategies represent promising future directions for improving melanoma immunotherapy outcomes.

Optimizing delivery systems and neoantigen selection may further enhance the therapeutic impact of mRNA melanoma vaccines.

Hybrid and personalized vaccine strategies represent promising future directions for improving melanoma immunotherapy outcomes.

Melanoma remains one of the deadliest cutaneous malignancies worldwide, and despite advances in systemic therapy, recurrence and treatment resistance remain frequent challenges. Following the success of COVID-19 mRNA vaccines, mRNA-based cancer vaccines targeting melanoma antigens have emerged as a promising therapeutic direction. This review summarizes current evidence on mRNA melanoma vaccines, focusing on two leading delivery platforms: lipid nanoparticles (LNPs) and dendritic cell (DC) vaccines. A comprehensive search of MEDLINE, Embase, and Scopus from 2015 to 2025 identified clinical trials, preclinical studies, and review articles evaluating mRNA vaccine constructs and delivery strategies. Completed clinical studies demonstrate that personalized LNP-formulated mRNA vaccines can enhance neoantigen-specific T-cell responses and improve recurrence-free survival, particularly when combined with immune checkpoint inhibitors. DC-based mRNA vaccines also show potent immunogenicity, with stronger responses observed when DC maturation is optimized. Ongoing trials continue to investigate next-generation LNP formulations, DC priming strategies, and personalized neoantigen approaches. Overall, current evidence indicates that both LNP and DC platforms can augment antitumor immunity by broadening T-cell responses and enhancing checkpoint inhibition. Continued refinement of delivery vehicles, neoantigen selection, and scalable manufacturing processes will be essential to realizing the full clinical potential of mRNA vaccines in melanoma.