RNA sequencing revealed the different transcriptional profiles of long-term cultured and short-term cultured CAR-T cells

Chimeric antigen receptor (CAR) T cells are known to be potent in recognizing and eliminating tumor cells. They induce marked responses in patients with refractory leukemia and lymphoma, but exhaustion is an inevitable obstacle important barrier for to persistant curative effect. CD19-targeted CAR incorporating the 4-1BB costimulation domain showed a lower tendency toward exhaustion during ex vivo expansion, and downstream differentiation was still observed with a prolonged culture time. We explored the transcriptional changes during the culture process using 4-1BB CD19-targeted CAR-T cells . In contrast to T cells (cultured 5 days in vitro) and short-term cultured (5 days) CAR-T cells, the pathway for regulation of the cytosolic calcium ion concentration was significantly upregulated in the long-term cultured (11 days) group. Overall design: We performed RNA-Seq differential expression analysis of T cells (cultured 5 days in vitro), short-term cultured (5 days) CAR-T cells and long-term cultured (11 days) CAR-T cells.