RESULTS

m6A-modified mRNA–LNP system enables in vivo CAR expression and is associated with antitumor immune responses (Scientific Reports, 2026)

In this study, Drs. Meng and Hara et al. developed a programmable mRNA–LNP delivery system incorporating N6-methyladenosine (m6A)-modified mRNA to enable in vivo CAR expression and antitumor immune responses. Using FAP-targeting CAR mRNA, we demonstrated that this approach was associated with altered RNA methylation states in immune cells and activation of immune-related pathways, including transcriptional signatures consistent with immune memory. The modular formulation enabled the incorporation of pH-responsive polybetaines while maintaining therapeutic activity. Furthermore, replacing FAP with cancer stem cell (CSC)-associated antigens, including EpCAM, LGR5, and CD133, preserved antitumor responses and was accompanied by suppression of tumor-intrinsic SPP1 signaling pathways. These findings establish a flexible platform for programmable mRNA-based cancer immunotherapy, integrating epitranscriptomic regulation, tunable nanoparticle composition, and antigen-specific CAR expression to support the development of novel therapeutic strategies for solid tumors.