Epigenetic priming to enhance CAR-T cell cytotoxicity in bladder cancer

We sought for new treatment strategies to improve response of urothelial carcinoma (UC) patients towards immune therapy. Epigenetic inhibitors may modulate expression of immune response regulators and alter the immune phenotype of UC cells. Thus, we determined whether longterm pretreatment of UC cell lines with the DNMT inhibitor decitabine (DEC) at low dosemight enhance killing by CAR-T cells. We engineered target-specific CAR-T cells recognizing EGFR and CD44v6 on UCC. To define underlying mechanisms we performed RNA Seq analysis for two UC cell lines treated accordingly. Overall design: UC cell lines BFTC-905 and UM-UC-3 were treated with 100 nM Decitabine and harvested after 3 days and 7 days. According DMSO controls were collected. RNA was submitted to RNA Seq Aanalysis to identify differentially expressed genes.