Extended Data Fig. 6: CD38 downregulation does not improve functionality of aged CAR-T cells.
From: Age-associated nicotinamide adenine dinucleotide decline drives CAR-T cell failure
Young and old CD8+ T cells were activated and transduced with an Her2 CAR or an Her2 CAR vector modified to contain an shRNA for CD38. On day 3, after transduction, CAR-T cells were expanded in the presence of IL-7 and IL-15 until day 7. In (a), protein levels of CD38 as assessed by flow cytometry on day 7. A representative histogram is shown in (b) (n = 3 biologically independent samples). (c) CD44/CD62L plots of young and old Her2 CAR T cells (Ctrl vs shRNA CD38) at day 7 of expansion. For (d), (e) and (f), old Her2 CAR-T cells, old Her2_shRNA CD38 CAR-T cells (expanded in the presence of NMN) or old Her2 CAR-T cells expanded in the presence of NMN + 78c were adoptively transferred at day 10 into mice bearing B16-HER2 tumors (n = 8 per group). Number of transferred CAR-T cells (CD45.1+) found in spleen after 32 days post-tumor engraftment is displayed in (D). Tumor growth is displayed in (E), while tumor size at endpoint is shown in (F). Data are represented as mean values +/- SEM. Statistical analysis was performed using one-way ANOVA.
