Fig. 6: CRS potential of DROP-CAR versus DEG-CAR T cells.
From: Drug-controlled CAR T cells through the regulation of cell–cell interactions
a, Schematic of the CRS potential assay, generated with BioRender.com. b, CRS potential assay by quantification of IL-6 production upon coculture of UTD, 2G-CAR, DEG-CAR and DROP-CAR T cells on day 12 after transduction with autologous monocytes and target tumor cells. Autologous monocytes were isolated (and donor T cell matched) on the assay day. Cocultures were established in the presence of 2.5 μM venetoclax and/or 1 μM lenalidomide (n = 3 HDs; two independent experiments). A two-way ANOVA was used to determine statistical significance by comparing all groups within each day. Day 1, DROP-CAR DMSO versus venetoclax, *P = 0.0113 and 0.0161. Day 2, DROP-CAR DMSO versus venetoclax *P = 0.0133; DROP-CAR DMSO versus lenalidomide *P = 0.028. Day 3, DROP-CAR DMSO versus venetoclax, *P = 0.0216; DROP-CAR DMSO versus lenalidomide + venetoclax, *P = 0.0146. Day 1, DEG-CAR DMSO versus venetoclax, *P = 0.0350; DEG-CAR DMSO versus lenalidomide, *P = 0.0464, **P = 0.0061. Day 2, DEG-CAR venetoclax versus lenalidomide, **P = 0.0043. Day 3, DEG-CAR DMSO versus lenalidomide + venetoclax, *P = 0.0711. NS, not significant. c, Control cultures of T cells and monocytes or T cells, monocytes and nontarget tumor cells (n = 3 HDs; two independent experiments). In a–c, data are reported as the mean ± s.e.m. Before all functional assays, the engineered T cells were rested and adjusted by mixing them with UTD cells for equivalent percentage CAR expression levels. A mix of 50% CD4+ T cells and 50% CD8+ T cells was used in the cocultures.
