ATAC-seq of colorectal cancer patient-derived xenograft (PDX) tumors treated with FAP-CAR mRNA-LNP therapy

This study investigates the therapeutic potential of an mRNA–lipid nanoparticle (LNP)-based strategy to deliver fibroblast activation protein (FAP)-specific chimeric antigen receptor (CAR) mRNA in colorectal cancer. Patient-derived xenograft (PDX) tumor models (PDX-1 and PDX-2) were treated by splenocytes (7SL1 knock-in) with FAP-CAR mRNA-LNPs, in comparison with PBS controls. ATAC sequencing of the tumor tissues was performed to profile transcriptional responses associated with treatment efficacy or resistance. Analysis revealed distinct chromatin accessibility programs, including activation of HOX gene clusters in resistant tumors, highlighting potential epigenetic mechanisms of therapeutic escape. Overall design: Tumor tissues were harvested from colorectal cancer PDX models following treatment with different regimens: PDX-1: PBS control vs. splenocytes (7SL1 knock-in) + FAP-CAR mRNA-LNPs. PDX-2: splenocytes (7SL1 knock-in) + FAP-CAR mRNA-LNPs.