Take Five: harmonization in personalized cancer vaccines for cancer immunotherapy.
Precision medicine provides a therapeutic framework that addresses the interindividual diversity in tumor genetics, immunological determinants of disease, and immune responsiveness. Among precision approaches, personalized cancer vaccines (PCVs) have gained attention as a promising strategy for inducing tumor-specific immunity by identifying patient-derived neoantigens. Despite encouraging clinical outcomes, the development of PCVs faces major challenges in optimizing antigen selection, delivery, immune activation, and clinical translation. This Review summarizes current advances in PCV research, covering tumor antigen classification, neoantigen prediction algorithms, and the evolution of delivery technologies such as peptide, dendritic cell, DNA, and mRNA-lipid nanoparticle platforms. We highlight the advantages of mRNA-lipid nanoparticle systems that enable rapid manufacturing, potent antigen expression, and integration with immunostimulatory cytokines. Furthermore, we discuss emerging combination strategies involving cytokine engineering and T cell modulation that provide new opportunities to enhance immunogenicity and therapeutic efficacy. Ultimately, we propose that the future maturation of PCVs will require a coordinated process across five interconnected dimensions: (1) advances in neoantigen prediction technologies, (2) rapid delivery of PCVs to patients, (3) an increase in anticancer efficacy through combination therapy strategies, (4) establishment of cost-effective manufacturing processes, and (5) regulatory innovation. In this Review, we conceptualize this multidimensional alignment as "Take Five," a unifying framework to bring precision, rhythm, and balance to next-generation cancer immunotherapy.