mRNA Vaccines on The Frontline: Targeting Neoantigens in Cancer Immunotherapy

Immunotherapy is an emerging technology in modern oncology that harnesses the body's immune system to target and destroy cancer cells. Neoantigen-based messenger RNA (mRNA) vaccines are one of the most promising emerging immunotherapeutic approaches, as they offer the unique advantages of high specificity, rapid manufacturing, and personalized treatment. Neoantigens are those antigens that are formed by mutations that happened in somatic cells and are not found in normal tissues and are highly immunogenic targets in cancer therapy. mRNA vaccine technology allows for the delivery of synthetic genetic material that encodes these neoantigens to cells, where the antigens are expressed within the cell and generates strong adaptive immune responses. This review focuses on the recent progress in neoantigen mRNA vaccine and its application in precision cancer immunotherapeutics. The article covers the structure and mechanism of mRNA vaccines, strategies for the identification of neoantigens, antigen presentation pathways, as well as the activation of both CD4+ and CD8+ T-cell responses. In addition, the review provides an overview of the development workflow of personalized mRNA cancer vaccines, from tumor sequencing to bioinformatics-based neoantigen prediction, to mRNA vaccine synthesis and strategies for clinical delivery. The clinical applications in melanoma, pancreatic, lung, glioblastoma and colorectal cancer are discussed, as are current clinical trials and investigational vaccine platforms. Furthermore, the review covers the key benefits of neoantigen mRNA vaccines, such as tumor specificity, low systemic toxicity, as well as ability to induce long-term immune memory and tolerance towards combination regimens. The difficulties of tumor heterogeneity, immune escape, manufacturing complexity and delivery are also addressed. In conclusion, neoantigen mRNA vaccines are a game-changing technology in personalized oncology with great potential for future clinical applications in cancer treatment and precision medicine