Engineering the future of precision cancer immunotherapy: Integrating neoantigen biology, engineered delivery platforms, and clinical translation.

This review focuses on the field of precision cancer immunotherapy, systematically describing the paradigm shift from traditional therapies to immune modulation strategies, with an emphasis on integrating interdisciplinary advances in neoantigen biology, engineered delivery platforms, and clinical translation. Tumor mutational burden and neoantigen burden serve as key biomarkers, which, combined with human leukocyte antigen typing and analysis of tumor immune microenvironment heterogeneity, provide the biological foundation for personalized immunotherapy. Engineering innovations cover delivery systems such as lipid nanoparticles and mRNA vaccines, as well as personalized modifications of CAR-T cells and synergistic strategies combining photothermal/photodynamic therapy with immune checkpoint blockade. The biomaterials field has developed intelligent delivery platforms and microenvironment-remodeling materials responsive to the tumor microenvironment (such as pH, hypoxia, and ROS), enhancing the specificity and safety of treatment. In the clinical translation of cancer treatment, challenges include insufficient accuracy of neoantigen prediction, production standardization, and safety issues, while advanced tools such as microfluidic technology, artificial intelligence modeling, and organ-on-a-chip provide directions for overcoming these bottlenecks. Future research will focus on the development of preventive vaccines, combination therapy strategies, and long-term immune monitoring to promote the clinical implementation of precision cancer immunotherapy. • Integrating neoantigen biology for precision cancer immunotherapy. • Engineered delivery platforms improve neoantigen stability, activation & targeting. • Personalized immunotherapy based on patient-specific tumor. • Scalable and effective precision cancer immunotherapy for future medicine.