RNA-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 with FAP-CAR mRNA-LNPs, including wild-type or 7SL1 knock-in splenocytes, in comparison with PBS controls. RNA sequencing of the tumor tissues was performed to profile transcriptional responses associated with treatment efficacy or resistance. Differential expression and pathway enrichment analyses revealed distinct immune and stromal gene programs, including HOX family transcription factor activation in resistant tumors. Overall design: Tumor tissues were harvested from colorectal cancer PDX models following treatment with different regimens: PDX-1: PBS control vs. splenocytes + FAP-CAR mRNA-LNPs (with 7SL1 knock-in splenocytes). PDX-2: PBS control vs. splenocytes + FAP-CAR mRNA-LNPs (with wild-type splenocytes or 7SL1 knock-in splenocytes).