Lantian Lu, Xuehan Lu, Wei Luo
Personalized cancer vaccines represent a revolutionary frontier in oncology, harnessing the unique genetic and molecular profile of individual tumors to elicit targeted immune responses. This review provides a comprehensive overview of the current landscape and future perspectives of neoantigen-based personalized cancer vaccines, encompassing peptide, mRNA, DNA, autologous dendritic cell, and viral or bacterial vector platforms. We further discuss the integration of immune adjuvants, delivery systems, and combinational strategies, particularly with immune checkpoint inhibitions, to overcome tumor-induced immune exhaustion and improve therapeutic efficacy. Despite significant clinical progress over the past decade in this space, major challenges remain in immunogenic neoantigens prediction, streamlining individualized vaccine manufacturing, and optimization of combinational regimens to maximize durable antitumor responses. By reviewing recent preclinical and clinical studies on neoantigen-based cancer vaccines, this review highlights key advances, identifies persistent translational bottlenecks, and underscores the need for biomarker-guided mechanistically informed trials to fully unleash the clinical potential of neoantigen-based personalized cancer vaccines in the era of precision immuno-oncology.