Extended Data Fig. 8: Safety assessment of Flt3L-secreting T cells and adjuvant therapy.
hHer2 transgenic mice were inoculated with 4 × 105 E0771-OVA-Her2 tumor cells and treated with transduced CAR T cells as per Fig. 6f. Mice were monitored for changes in weight. Alternatively, sera and organs were assessed at 48 hours post adjuvant therapy for toxicity studies. a, Liver function and/or damage was assessed by serum alanine transaminase (ALT), aspartate aminotransferase (AST), total albumin, bilirubin, and gamma glutamyl transferase (GGT) levels. b, Kidney function and/or damage was assessed by serum urea and creatinine levels. c, Sera were assessed for levels of IFN-γ, IL-1β, IL-6, GM-CSF, G-CSF, MCP-1 and TNF cytokines. d, Percentage weight change relative to day 0 measurements. Dotted line (90%) indicates the maximum ethical limit allowed for weight reduction. Arrows indicate adjuvant administration (NT n = 5 mice, CAR T and FL + Isotype n = 6 mice/group, CAR T and FL + adjuvants n = 8/group). e, Representative hematoxylin and eosin histology staining of cerebellum, liver, kidney, lung and spleen of control non-treated (NT), CAR T or CAR T FL adjuvant treated mice (3 mice/group). f, Sera were assessed for antinuclear antibodies as an indication of autoimmunity (n = 5 mice/group). Sera from NZB/W (with proteinuria; n = 3) and C57BL/6 mice (n = 3) immunized with an irrelevant antigen (NP-KLH) were respectively used as positive and negative controls. Bars represent mean ± SEM, a–c Symbols represent individual mice, 1-way ANOVA.
