Neoantigen Vaccines in Cancer Prevention.

Abstract

Recent advances in cancer immunotherapy have established neoantigen-based vaccines as a promising approach to cancer prevention. Unlike tumor-associated antigens, neoantigens originate exclusively from somatic mutations, thus enabling tumor-specific targeting without harm to normal tissues. This distinctive feature promotes robust immune responses while reducing the risk of autoimmune side effects. Developing standardized "off-the-shelf" vaccines targeting shared neoantigens offers a scalable strategy for cancer prevention, particularly benefitting genetically predisposed high-risk populations. These vaccines can be administered to high-risk individuals before malignant transformation to potentially intercept cancer development through early immune activation. Advances in next-generation sequencing and computational biology have increased the accuracy of neoantigen prediction, while advances in vaccine delivery platforms have boosted vaccine efficacy. The integration of neoantigen-based vaccines with immune checkpoint inhibitors, immune stimulants, and classic chemopreventive agents has a synergistic potential to improve cellular immunity. This review examines biological mechanisms, clinical development, and future directions of neoantigen-based vaccines in cancer prevention, emphasizing their clinical potential to revolutionize risk-reduction strategies.