single cell RNA-sequencing analysis of human SUV39H1-knockout CAR T compared to control CAR T cells (mock) in a xenograft model of lung adenocarcinoma
We have observed that the inactivation of SUV39H1 enhances 41BBz-CAR T cell long-term persistence, providing protection against tumor relapses and rechallenges in a xenograft mouse model of lung adenocarcinoma. The purpuse of this study is to investigate the transcriptomic differences of lung-infiltrating SUV39H1 knock-out versus mock 41BBz-CAR T cells by single cell RNA sequencing at days 8 and 28 after CAR T cell infusion. Overall design: NSG mice that received intravenous injections of tumor cells (A549) ectopically expressing CD19 that develop tumors in the lungs were treated 21 days later with 0,9 million of 41BBz-CAR T cells (i.v.) that were SUV39H1-knockout (CRISPR/Cas9 technology) or controls CAR T cells (same CRISPR/Cas9 protocol with a sgRNA that does not have any complimentary sequence in the genome). CAR T cells were isolated from lungs at day 8 and 28 after infusion, T-cells were FACS sorted and subjected to Chromium 10× Single-Cell 3' mRNA sequencing (three biological replicates for each condition and timepoint).