Cancer vaccines based on mRNA: Hype or hope?

The key role of mRNA as an intermediate molecule between DNA and protein expression has first been described in the last century. Yet, its application as a therapeutic molecule to instruct cellular functions has only been fully exploited in the last decade. As a result of progress made in the manufacturing of nonimmunogenic mRNA molecules and their efficient delivery into cells, the activity of mRNA in the cellular cytoplasm allows fast, high, and transient expression of proteins. mRNA does not integrate or replicate (except for self-amplifying mRNA) and thus lacks neoplastic behavior. Though advances in mRNA cancer vaccination was a tedious process with several hurdles, results have shown the potential of mRNA as a low toxicity, flexible, versatile, robust, time, and cost-efficient vaccine platform. Further, these pioneering activities enabled the development at unprecedented speed of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), marking a critical turning point in the COVID-19 pandemic. The global reputation of SARS-CoV2 mRNA vaccines is likely to propel successful adaptation of mRNA for cancer vaccination. We introduce the concept of cancer vaccination and the lessons learned so far on using mRNA as a technology platform for cancer vaccination.