Therapeutic vaccines offer a targeted approach to enhancing anti-tumor immunity with minimal systemic toxicity. Despite advancements in surgery, chemotherapy, radiation, and immunotherapy, colorectal cancer (CRC) remains a major clinical challenge, particularly due to the limited efficacy of immune checkpoint inhibitors outside the MSI-H subgroup. In this comprehensive review summarizes the emerging vaccine modalities for CRC, including peptide, nucleic acid, cell-based, vector-driven, and nanotechnology platforms. We discuss the barriers posed by tumor immune evasion and heterogeneity, and highlight innovative strategies designed to improve vaccine efficacy. Finally, we explore recent clinical developments and translational opportunities that position therapeutic vaccines as a promising component of future CRC immunotherapy.
Keywords: clinical translation; colorectal cancer; immune evasion; immunotherapy; nanovaccines; neoantigens; therapeutic vaccines; tumor microenvironment.