mRNA 负载脂质纳米颗粒在癌症疫苗中的关键临床前沿

Cancer vaccines are promising, but clinical translation is constrained by inefficient antigen delivery and suboptimal immune activation. Lipid nanoparticles (LNPs)-validated for potency and safety in COVID-19 mRNA vaccines-offer a versatile, scalable, and immunogenic platform. Key barriers persist: precise targeting of tumors or lymphoid tissues, efficient intracellular mRNA release, and the immunosuppressive tumor microenvironment. This review synthesizes design principles for mRNA-loaded LNPs, emphasizing lipid chemistry, organ-selective biodistribution, and nano-engineering strategies that strengthen antigen presentation and T-cell priming. We also examine combination approaches with checkpoint blockade, chemotherapy-induced immunogenic cell death, and molecular adjuvants. Clinically, signals of efficacy are emerging-most notably the KEYNOTE-942 study, in which mRNA-4157 combined with pembrolizumab showed a sustained improvement in recurrence-free survival at 5 years compared with pembrolizumab alone-highlighting both the potential and the remaining questions for this modality. Finally, we outline manufacturing and regulatory considerations and map future directions-including thermostable formulations, self-amplifying RNA, and AI-guided lipid discovery-to address translational bottlenecks and expand global access to LNP-based cancer vaccines.