Personalized Neoantigen Vaccines in Melanoma: Current Workflow and Adjuvant Opportunities

Abstract

Personalized neoantigen vaccines represent a promising advance in cancer immunotherapy, with melanoma serving as a leading model due to its high mutational burden and immunogenicity. Unlike shared tumor-associated antigens, neoantigens arise from tumor-specific somatic mutations and are absent from normal tissues, enabling highly selective immune targeting. Advances in immunogenomic workflows now allow rapid identification of patient-specific neoantigens through integrated tumor–normal sequencing, transcriptome analysis, HLA typing, and computational epitope prediction, followed by individualized vaccine manufacturing. Multiple vaccine platforms, particularly mRNA-based approaches, have demonstrated robust induction of neoantigen-specific CD4⁺ and CD8⁺ T cell responses. Emerging evidence suggests that the adjuvant setting represents a critical window for clinical benefit, as vaccination after surgical tumor removal may enable elimination of microscopic residual disease and durable immune surveillance. Incorporation of presentation-informed strategies, including immunopeptidomics and refined computational models, may further improve target selection by prioritizing neoantigens that are truly presented on tumor cells. Together, these developments establish personalized neoantigen vaccination as a clinically feasible and biologically compelling strategy in melanoma, with potential applicability to other high-risk solid tumors.

Keywords: Neoantigens, Tumor antigens, Cancer vaccines, Immunotherapy