Fig. 6. Descartes-08 cells with TCR-knockout significantly blocked disseminated MM1S tumor growth in NSG mice, leading to prolonged host survival.
NSG mice receiving MM1S-luc cells (2 × 106 cells per mouse i.v.) at day 0 were randomized into treatment groups (n=4 per group) on day 6. On days 7, 14, 21 and 28, T-cells were thawed from cryovials, washed, and resuspended for administration via i.v. injection with vehicle, 20 × 106 mock-transfected control TCR knockout (KO) CD8+ (ctrl CD8+) or Descartes-08 cells (showing 67% BCMA CAR expression by FCM analysis). On day 13, 20 and 27, all mice were treated with 60 mg/kg cyclophosphamide. a Bioluminescence (BLI) images (MM1S-fluc growth) of mice in each group on day 27 (after 3 doses of Descartes-08 cells or controls). Tumor growth (b, means ± SDs) and survival (c) of animals are shown through timeframe of study. b-c Each of the 4 dosing days was marked with an arrow. Median survival days are 43 (vehicle), 44 (ctrl CD8+ T cells) and 69 (Descartes-08 CAR T) days. Survival curves of TCR KO Descartes-08 (Descartes-08) was significantly different (P<.0001) compared with paired control TCR KO CD8+ T cells (ctrl CD8+ T) by log-rank (Mantel-Cox) test. Tumor growth curves were analyzed by 2-way ANOVA after log-transformation of data. Survival curve in animal model was plotted using the Kaplan-Meier method and compared by the log-rank test. ****P<.0001