Considerations on the design of lipid-based mRNA vaccines against cancer

Throughout the last decades, mRNA vaccines have been developed as a cancer immunotherapeutic and the technology recently gained momentum during the COVID-19 pandemic. Recent promising results obtained from clinical trials investigating lipid-based mRNA vaccines in cancer therapy further highlighted the potential of this therapy. Interestingly, while the technologies being used in authorized mRNA vaccines for the prevention of COVID-19 are relatively similar, mRNA vaccines in clinical development for cancer vaccination show marked differences in mRNA modification, lipid carrier, and administration route. In this review, we describe findings on how these factors can impact the potency of mRNA vaccines in cancer therapy and provide insights into the complex interplay between them. We discuss how lipid carrier composition can affect passive targeting to immune cells to improve the efficacy and safety of mRNA vaccines. Finally, we summarize strategies that are established or still being explored to improve the efficacy of mRNA cancer vaccines and include next-generation vaccines that are on the horizon in clinical development.