Fig. 6: Amph-mimotope vaccine enhances FMC63-mCAR-T therapy in an immunocompetent hCD19+ Eμ-Myc B-ALL/lymphoma mouse model. | Nature Biomedical Engineering

Fig. 6: Amph-mimotope vaccine enhances FMC63-mCAR-T therapy in an immunocompetent hCD19+ Eμ-Myc B-ALL/lymphoma mouse model.

From: Directed evolution-based discovery of ligands for in vivo restimulation of chimeric antigen receptor T cells

Fig. 6

a,b, Real-time whole animal imaging tracking disease progression. C57BL/6 albino mice were lympho-depleted and injected with 0.5 × 106 hCD19+Luc+ Eμ-Myc cells. On day 4, mice were adoptively transferred with 2 × 106 FMC63-mCAR-T cells and then vaccinated 1 day later with 10 μg amph-F12-A1 + 25 μg CDG (n = 8 mice per group). Shown are whole animal imaging at indicated times (a) and quantification of total photon counts over time in each group (*P = 0.0100; ****P < 0.0001) (b). c, Enumeration of circulating CAR-T cells or control T cells by flow cytometry over time (n = 8 mice per group at days 0 and 11; for day 18 n = 5 for control T cells, n = 7 for FMC63-mCAR-T, n = 8 for FMC63-mCAR-T + Vax) (****P < 0.0001). d,e, Immunophenotype of circulating CAR-T cells on days 11 and 18. Shown are the representative flow cytometry plots (d) and percentages of effector/effector memory (EM; CD44+CD62L−) and central memory (CM; CD44+CD62L+) CAR-T cells (e) (n = 8 mice per group at day 11; n = 7 for FMC63-mCAR-T and n = 8 for FMC63-mCAR-T + Vax at day 11) (day 11 effector/EM **P = 0.0001; CM ****P < 0.0001; day 18 effector/EM ***P = 0.0007; CM ***P = 0.0004). f,g, Cytokine polyfunctionality of circulating CAR-T cells on day 11. Shown are representative contour plots (f) and percentages of cytokine-secreting CAR-T cells (g) (n = 8 mice per group) (IFNγ+, ***P = 0.0005; TNF+, **P = 0.0017; IFNγ+TNF+, ***P = 0.0006). h, The overall survival of Eμ-Myc mice under various treatment regimens (n = 8 mice per group) (untransduced T versus FMC63-mCAR-T, **P = 0.0015; untransduced T versus FMC63-mCAR-T + Vax, ***P = 0.0002; FMC63-mCAR-T versus FMC63-mCAR-T + Vax, **P = 0.0016). Error bars show mean ± 95% CI. *P = 0.0100; **P < 0.01; ***P < 0.001, ****P < 0.0001, by two-way ANOVA with Tukey’s post-test for b, by one-way ANOVA with Tukey’s post-test for c, by two-sided unpaired t-test for e and g, and by log-rank (Mantel–Cox) test for h.

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