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.

Keywords

chimeric antigen receptor T cells (CAR-T) / messenger RNA (mRNA) / mRNA delivery system / mRNA-based CAR-T immunotherapy

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2023 2023 The Authors. Interdisciplinary Medicine published by Wiley-VCH GmbH on behalf of Nanfang Hospital, Southern Medical University.