Toward cancer immunoprevention: what are the prospects for therapeutic vaccines?

Therapeutic cancer vaccines represent a promising immunotherapy approach aimed at treating existing cancers by stimulating the patient's immune system to target tumor cells. Unlike prophylactic vaccines, therapeutic vaccines are administered after cancer diagnosis and focus on inducing specific cytotoxic CD8⁺ T cell responses against tumor-associated antigens or tumor-specific neoantigens. These antigens are presented by antigen-presenting cells, such as dendritic cells, to activate an immune attack. However, the efficacy of therapeutic vaccines is often limited by immune tolerance, tumor heterogeneity, and an immunosuppressive tumor microenvironment, necessitating combination with other treatments like immune checkpoint inhibitors or chemotherapy. Multiple vaccine platforms are under investigation, including peptide/protein-based, DNA/messenger RNA (mRNA)-based, dendritic cell vaccines, viral vector vaccines, and personalized neoantigen vaccines that leverage next-generation sequencing for precision targeting. Clinical trials target a range of cancers, including melanoma, gynecologic, breast, pancreatic, liver, glioblastoma, and lung cancers, with results showing immune activation but modest clinical efficacy. Key challenges include immune evasion, variability in patient response, manufacturing complexities, high cost, and lack of predictive biomarkers. Technological advances in nanoparticle delivery, potent adjuvants, mRNA platforms, and combination immunotherapies are being explored to enhance vaccine performance. In low-resource settings, barriers such as limited access to advanced diagnostics and clinical trials necessitate tailored strategies to ensure equitable vaccine deployment. Overall, therapeutic cancer vaccines hold potential to become integrated into standard oncology protocols, especially for adjuvant therapy and recurrence prevention, with an emphasis on personalized and accessible immunotherapies to transform cancer management globally.