mRNA therapy is a novel anticancer strategy based on in vitro transcription (IVT), which has potential for the treatment of malignant tumors. The outbreak of the COVID-19 pandemic in the early 21st century has promoted the application of mRNA technologies in SARS-CoV-2 vaccines, and there has been a great deal of interest in the research and development of mRNA cancer vaccines. There has been progress in a number of key technologies, including mRNA production strategies, delivery systems, antitumor immune strategies, etc. These technologies have accelerated the progress and clinical applications of mRNA therapy, overcoming problems encountered in the past, such as instability, inefficient delivery, and weak immunogenicity of mRNA vaccines. This review provides a detailed overview of the production, delivery systems, immunological mechanisms, and antitumor immune response strategies for mRNA cancer vaccines. We list some mRNA cancer vaccines that are candidates for cancer treatment and discuss clinical trials in the field of tumor immunotherapy. In addition, we discuss the immunological mechanism of action by which mRNA vaccines destroy tumors as well as challenges and prospects for the future.

mRNA cancer vaccines show therapeutic potential for malignant tumors, including hepatocellular carcinoma (HCC). We optimized and synthesized stable mRNA encoding costimulator Oxford 40 ligand (OX40L). For systemic delivery, OX40L mRNAs were loaded into lipid nanoparticles (LNPs). The expression and costimulatory effects of OX40L were investigated in vitro. OX40L was expressed on the cell surface and costimulated T cells. In vivo, intratumoral injection of LNPs encapsulating OX40L mRNAs significantly reduced tumor growth and increased the survival of mice bearing H22 tumors. Importantly, CD4+ and CD8+ T cells were significantly increased in the OX40L mRNA group in vivo. Taken together, our findings provide a promising clinical strategy for immunotherapy for HCC using mRNA vaccines.

Infectious diseases have always threatened human life, but with the development of vaccines, effective strategies for preventing and controlling these diseases have become available. The global outbreak of COVID-19 ushered in the advent of mRNA vaccine technologies, which quickly led to the introduction of mRNA vaccines effective against SARS-CoV-2. The success of this approach has stimulated research into the use of mRNA vaccines in the fight against other emerging as well as remerging infectious diseases. This review examines the constructive strategies and delivery systems used in mRNA vaccines and provides an overview of current clinical trials of those vaccines in the prevention of infectious diseases. The underlying mechanisms of mRNA vaccines are also discussed, including the double-edged sword of the innate immune response. Finally, the challenges but also the potential of mRNA vaccines are considered.

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