Research Progress in mRNA Cancer Vaccines: Immunogenicity Regulation, Optimization of Lipid Nanoparticle Delivery Systems, and Challenges in Non-Hepatic Targeting

In 2022, approximately 20 million new cancer cases and 9.7 million cancer-related deaths were reported globally, with lung cancer representing the most prevalent form and the leading cause of cancer-related mortality. Traditional chemotherapy has limitations like poor targeting and severe toxic side effects, while mRNA cancer vaccines are a research hotspot for high safety and rapid antigen translation, though facing suboptimal targeting. This review summarizes recent progress and future directions in mRNA cancer vaccine development. It first introduces the definition and mechanism of mRNA cancer vaccines, analyzes the "double-edged sword" immunogenicity of in vitro transcribed (IVT) mRNA (activation boosts efficacy, but excessive activation risks harm) and its regulatory strategies (e.g., nucleoside modification, UTR optimization). Focusing on lipid nanoparticle (LNP) delivery to address naked mRNA degradation, it discusses optimization of targeting and efficiency via novel lipid screening, ratio adjustment, surface modification, and administration routes. It also explores mechanisms, strategies, and challenges of non-hepatic targeting (e.g., pulmonary mucus barrier). Despite progress, breakthroughs are needed to overcome physiological barriers and LNP toxicity for advancing clinical translation.