Therapeutic Cancer Vaccines: Mechanisms, Clinical Progress, and Future Directions.

Therapeutic cancer vaccines have emerged as a promising approach in cancer immunotherapy, aiming to stimulate the immune system to recognize and eliminate malignant cells. Despite this potential, clinical efficacy has remained variable across multiple vaccine platforms. This review synthesizes completed clinical trials evaluating major therapeutic cancer vaccine modalities, including peptide-based, nucleic acid--based, dendritic cell, whole cell, and viral and bacterial vector--based vaccines, with a focus on safety, immunogenicity, and clinical outcomes for diverse tumor types. Overall, these vaccines demonstrate a favorable safety profile; however, clinical efficacy as monotherapy has been limited. Clinical outcomes vary by platform and tumor type and are influenced by factors such as antigen selection, tumor heterogeneity and immunosuppressive tumor microenvironment (TME). Recent advances in antigen design, vaccine technologies, and combination strategies are redefining the role of therapeutic cancer vaccines in oncology. Future progress will depend on optimizing their integration with standard treatment modalities, particularly immune checkpoint inhibitors.