mRNA and Peptide Vaccines in Melanoma—Current Landscape and Future Direction

Immune checkpoint inhibitors have transformed the treatment landscape for advanced melanoma in the past 15 years, delivering unprecedented and durable survival benefits. This success has propelled the development of complementary immune-directed therapies, including cancer vaccines. Among these, synthetic long peptide (SLP) and mRNA vaccine platforms have emerged as highly promising. Advances in next-generation sequencing technology, alongside computational neoantigen algorithm predictions, have enabled patient-specific neoantigen identification to improve vaccine immunogenicity and enhance therapeutic efficacy. Off-the-shelf and personalised SLP and mRNA vaccines have demonstrated the ability to induce robust antigen-specific T-cell responses and modulate the tumour microenvironment. Mechanistically, cancer vaccines synergise with immune checkpoint inhibition. This review outlines the current clinical development of mRNA and peptide vaccines in melanoma, highlighting the significant promise to synergise with immune checkpoint inhibition to enhance efficacy without adding to the systemic toxicity profile. The neoadjuvant setting, characterised by intact tumour antigens and draining lymphatic architecture, offers a compelling biological context for leveraging cancer vaccines for enhanced immune priming and response assessment. Collectively, the rapid advances in technology and emerging clinical data position cancer vaccines as a promising therapy capable of improving immunotherapy in Stage III and IV melanoma.