Therapeutic Colorectal Cancer Vaccines: Emerging Modalities and Translational Opportunities

Abstract

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.

Figure 1

Progression, Classification, Screening of Colorectal Cancer (CRC). The development of colorectal cancer progresses through four stages: dysplasia, adenoma, carcinoma, and metastasis, driven by a variety of genetic and molecular pathways. Depending on the disease stage and severity, specific treatment approaches are recommended for CRC patients. Classification of CRC into Consensus Molecular Subtypes (CMS) provides valuable clinical prognostic and predictive information to guide therapy decisions. Advances in screening technologies have greatly improved the precision of CRC detection and treatment planning [25]. (Created in Biorender; Palaniyandi (2025) https://app.biorender.com/i-67fc6e5ec8be8eb93162a9c2-fig1crc (accessed on 25 March 2025)).

Figure 2

Modalities for Colorectal Cancer Vaccines. A schematic representation illustrating the various strategies employed in the development of colorectal cancer vaccines and their mechanisms for activating the immune system. These modalities promote immune-mediated tumor neutralization through diverse immunological pathways. (Created in Biorender; Palaniyandi (2025) https://app.biorender.com/i-67fcc6f74856de77a515ab6d-fig3-crc (accessed on 27 March 2025).