Viral Vector-Based Personalized Cancer Vaccine: Current Mechanisms, Clinical Evidence and Future Directions

Cancer immunotherapy has become a more popular method to treat cancer. It uses patients’ own immune system to recognize and eliminate cancer cells. Within the different forms of immunotherapy, personalized cancer vaccines (PCVs) stand out as a revolutionary option as they target individual-specific neoantigens. This allows for precise interventions that can trigger long-term immune responses. PCVs are usually developed using three major platforms: mRNA, DNA, and viral vector vaccines. This review focuses on the viral vector strategies, with representative examples of NOUS-PEV, GRANITE, and TG4050. Viral vector vaccines are very good at delivering antigens effectively, trigger strong immune response, and activate both innate and adaptive immunity, leading to strong CD8+ and CD4+ T cell responses. Early clinical trials have shown encouraging safety and immunogenicity, as well as signals of efficacy across different tumor types. However, there are still obstacles remaining. This includes limited accuracy of neoantigen prediction, complex manufacturing process, and tumor-mediated immunosuppression. Future progress is likely going to rely on multi-omics integration, AI-driven epitope prioritization, innovative delivery platforms, and combination strategies with other immunotherapies. Collectively, PCVs have the potential to become the cornerstone of precision oncology to provide personalized and durable therapeutic benefits to cancer patients.