mRNA‐based chimeric antigen receptor T cell therapy: Basic principles, recent advances and future directions

Abstract Non‐viral vector chimeric antigen receptor (CAR)‐T cells have garnered increasing attention due to their ability to efficiently eradicate cancer cells while mitigating undesirable side effects. However, the current methods for engineering chimeric antigen receptor T (CAR‐T) cells employ viral vectors that result in permanent CAR expression and potentially severe negative impacts. As a solution to these challenges, triggering transitory expression of CARs in T cells via messenger RNA (mRNA) has emerged as a promising strategy. Currently, electroporation is a common method used to introduce the mRNA encoding the CAR into the T cells. Moreover, there has been increasing attention on the exploration of innovative mRNA delivery systems, including lipid, polymer‐based nanoparticle, exosomes and peptide transduction domains. Additionally, we also explored the functions of different types of mRNA in mRNA‐based CAR‐T cell therapy. The auxiliary mRNA, exemplified by systems such as megaTAL and nuclease transposon systems, demonstrates its capacity to extend CAR‐T cell viability and survival. This perspective offers the current state of mRNA‐based CAR‐T cell therapy and provides valuable insights into future research avenues.