Review Article: mRNA CARs: An Emerging New-Old Idea

Chimeric antigen receptor (CAR) T cell therapy has transformed cancer immunotherapy. Still, conventional viral vectors carry risks of insertional mutagenesis, are costly to manufacture, and can cause persistent on-target/off-tumor toxicity. Messenger RNA (mRNA) platforms offer a nonintegrating, transient alternative that enables rapid, modular expression of CARs and accessory molecules and can be extensively optimized. mRNA CAR T cells can be manufactured in days, and their transient expression allows repeat dosing and mitigates prolonged toxicity. Preclinical studies show that electroporation or lipid nanoparticle delivery can generate potent CAR-engineered immune cells. Beyond oncology, transient mRNA CARs are explored for autoimmune diseases such as systemic lupus erythematosus, lupus nephritis and myasthenia gravis, where short-lived CAR expression can reset autoreactive B-cell compartments while avoiding long-term immunosuppression. Emerging delivery strategies, including targeted lipid nanoparticles that program T cells in vivo, could eliminate the need for ex vivo cell manufacture and extend CAR therapy to fibrosis and regenerative medicine. Collectively, these developments position mRNA-engineered CARs as a flexible, safer and scalable platform that complements or potentially surpasses viral CAR technologies in oncology, autoimmunity and beyond.

Abstract from PubMed (PMID 42962193). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.