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Fig. 3 | Molecular Cancer

Fig. 3

From: Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study

Fig. 3

h1218-CART19 recognize and kill relapsed FMC63-CAR19+ Nalm6. A Schematic representation of a B cell lymphoma/leukemia cell accidentally transduced with the FMC63-CAR19 lentivirus during manufacturing that leads to epitope masking and resistance to FMC63-based CART19. B FMC63 expression level on Nalm6 cells measured by flow cytometry. C IL-2 cytokine release quantification by ELISA 24 h after CART and cancer cell co-culture at a E:T ratio of 5:1 (n = 2 donors). All values determined as negative by comparison to the standard curve are shown as zero. D 48-h CART cytotoxicity against Nalm6-FMC63 at various E:T ratios (n = 2 donors) by flow cytometry. E Tumor growth in the presence of CART cells over 10 days (n = 3 donors) by flow cytometry. (Left) Fold change over time of Nalm6-FMC63 cells compared to day 0 counts. (Right) Nalm6-FMC63 fold change on day 6. F (Left) Schematic of the xenograft mouse model: 1 × 106 luciferase+ Nalm6-FMC63 cancer cells were engrafted 5 days before intravenous injection of 0.75 × 106 UTD or CART cells. (Right) Tumor burden over time in mice bearing Nalm6-FMC63 with UTD (n = 5), FMC63-CART19 (n = 5), or h1218-CART19 (n = 5). Bolded line represents the median of each group. G. Overall survival in mice bearing Nalm6-FMC63 (p = 0.0016). All bar graphs and cytotoxicity curves are represented as mean ± SEM. One-way ANOVA was performed with Tukey correction for multiple comparisons; survival curves were compared using the log-rank (Mantel-Cox) test; **** p < 0.0001, *** p < 0.001, ** p < 0.01, and * p < 0.05. All bar graphs are represented as mean ± SEM. All the experiments were repeated at least twice

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