RNA-seq of tumors from mice treated with FPC (5-FU, anti-PD-1 antibody, and anti-CTLA-4 antibody), mRNA–LNP and KDM5B inhibitors.

However, significant challenges remain, particularly with respect to its application to solid tumours and the high cost of manufacturing. To address these limitations, the development of mRNA–lipid nanoparticle (LNP) therapeutics capable of generating CAR-T cells in vivo has attracted increasing attention.

In this study, we administered LNP-formulated mRNA encoding a fibroblast activation protein (FAP)-targeting CAR in a mouse tumour model and investigated how tumour-resident cells alter their gene expression profiles in response. We further examined how KDM5B inhibition influences the antitumor effect in combination with in vivo CAR-T therapy.