Bridging clinical gaps in personalized cancer neoantigen vaccines

Personalized cancer neoantigen vaccines (PCV) represent an individualized form of immunotherapy. Neoantigens encoded by individual tumor mutations offer precise targets for robust, tumor-specific immunity. Next-generation sequencing and advanced bioinformatics have facilitated personalized neoantigen discovery, while progress in vaccine platforms has enabled optimization of delivery technologies and generated a versatile and scalable framework for neoantigen vaccine therapy, allowing therapeutic administration across diverse clinical settings. The integration of neoantigen vaccines with other treatment modalities requires careful consideration of timing, sequencing, and synergistic potential. In this review, we synthesize emerging data highlighting tumor indications suitable to investigate PCVs, define optimal clinical settings for vaccine administration, and discuss combinatorial regimens to enhance efficacy, as well as the timing and sequencing in multimodal treatment, aiming to address key translational opportunities and challenges essential to deploying neoantigen vaccines broadly in the clinic.