Juwei Gao, Yue Sun, Zijing Han, Huiwen Zhang, Mingwei Sun, Shujun Liu, Bo Zhang
These advances provide an integrated framework for developing next-generation therapeutic cancer vaccines and advancing precision cancer immunotherapy.
BACKGROUND: With the rapid advancements in oncology, immunology, and molecular biology, immunotherapy has emerged as a cornerstone of anti-tumor treatment, complementing traditional modalities such as surgery, radiotherapy, and chemotherapy. Therapeutic cancer vaccines are a promising immunotherapy strategy that deliver tumor-associated antigens or neoantigens to prime naive T cells and generate long-lived memory cells for durable anti-tumor immunity. Recent advances in neoantigen identification, mRNA technology, biomaterial delivery and combination immunotherapy accelerate the development of personalized cancer vaccines. However, their clinical efficacy remains suboptimal, limited by poor immunogenicity, tumor heterogeneity, immune escape and immunosuppressive TME. OBJECTIVES: This review classifies therapeutic cancer vaccines by antigen source and design strategy, analyzes key biological barriers limiting efficacy, summarizes clinical trial evidence, and discusses strategies to overcome these bottlenecks. METHODS: We systematically reviewed published literature regarding cancer vaccine design, delivery platforms, clinical trials and combination immunotherapy. RESULTS: Multiple biological obstacles restrict vaccine efficacy. Novel approaches including computational antigen design, advanced RNA platforms, optimized delivery, biomarker-guided vaccination and rational combination therapy can mitigate these barriers. CONCLUSIONS: These advances provide an integrated framework for developing next-generation therapeutic cancer vaccines and advancing precision cancer immunotherapy.