mRNA Vaccine Platforms in Cancer Immunotherapy: Mechanisms, Innovations, and Clinical Prospects

Cancer is one of the primary causes of global health issues and deaths. To address this burden and to develop alternatives to chemotherapy and radiation, innovative and targeted treatment strategies must be developed. One way to do this is through cancer immunotherapy, which is quickly becoming an innovative approach that uses the body's immune system to identify and destroy cancer cells. Within the immunotherapy realm, mRNA vaccines have quickly gained full attention due to their safety, adaptability, and rapid timeline to produce. The mechanism of action of mRNA vaccines for cancer is based on the introduction of synthetic mRNA containing either tumorrelated or tumor-specific antigens that induce local generation of the antigenic protein once introduced into the host cell, especially dendritic cells. In turn, the target proteins generated from the injected synthetic mRNA are presented through Class II Histocompatibility Complex (MHC) pathways, which promote both cellular- (CD8+ cytotoxic T cells) and humoral-mediated immunity targeting tumor cells. A significant advantage of the mRNA vaccination approach is to create a potent and specific anti-tumor immune response without causing significant harm to healthy tissues (non-infectious); thus supplying a promising platform for cancer therapy. In the past several years, advances in mRNA design capabilities, including both structural optimization and the addition of modified nucleosides, and advances in effective vaccine delivery systems (such as lipid nanoparticles), have provided substantial improvements in stability and efficacy of delivery of mRNA vaccines. Furthermore, personalized mRNA vaccines targeting patient-specific neo-antigens represent a significant breakthrough in the evolution of precision medicine. Ongoing challenges with mRNA vaccines apply to four general areas: (1) mRNA instability due to chemical and physical properties, (2) delivery efficiencies of mRNA, (3) tumor heterogeneity, and (4) immunosuppressive tumor microenvironments. Ongoing clinical research and clinical trials are evaluating ways to overcome these hurdles as well as evaluation of combination therapies of mRNA vaccines with immune checkpoint inhibitors and/or other therapies. In summary, mRNA vaccines represent a unique and rapidly evolving strategy within the field of cancer immunotherapy and have the ability to dramatically change the future of cancer treatments and create more options for targeted and personalized therapies for individuals with cancer