Messenger RNA (mRNA) has gained increasing attention as a valuable tool to cure various human diseases, particularly malignant tumors. Such growing interest has been triggered largely by the phenomenal clinical success of mRNA vaccines developed using lipid nanoparticle (LNP) technology against COVID-19. mRNA may be used to produce cancer immunotherapies in numerous different ways, including cancer vaccines to induce or enhance immunity to tumor-specific antigens (TSAs) or tumor-associated antigens (TAAs). mRNA can also be used to adoptively transfer T-cells for the expression of antigen receptors, such as chimeric antigen receptors (CARs), therapeutic antibodies, and immunomodulatory proteins to re-engineer the tumor microenvironment. However, the therapeutic potential of mRNA-based cancer immunotherapy is not fully utilized due to a few limitations, such as mRNA instability, production of immunogenicity, and a lack of efficient in-vivo delivery methods. This review provides an overview of the current advancements and future directions of mRNA-based cancer therapies, including various delivery routes and therapeutic platforms. It addresses the mechanistic basis of mRNA cancer vaccines, non-replicating and self-amplifying mRNA, as well as their clinical development, personalized vaccines, and applications of mRNA for encoding antigen receptors, antibodies, and immunomodulatory proteins. Moreover, the review addresses nanoparticle-based platforms, such as lipid nanoparticles (LNPs), polymeric nanoparticles, and peptide-based nanoparticles, all used to improve the therapeutic effectiveness of mRNA-based drugs by improving their targeted delivery to tissues. This review aims to provide insights into the use of state-of-the-art mRNA-based cancer immunotherapy.
