Figure 5
Long-term in vivo antitumor activity of TERT mRNA delivered to CAR T cells. (a) Schema of in vivo study demonstrating the antitumor activity of transduced T cells in a disseminated human B-cell malignancy xenogeneic NPG/Vst mice model (GFP-T: n=6, CAR-T: n=6, CI-CAR-T: n=6, TERT-CAR-T: n=6). (b) Antitumor activity of TERT mRNA delivery CAR T cells in NPG/Vst mice by weekly in vivo bioluminescent imaging. (c) Summary of the bioluminescence signal (relative Fluc activity in p s−1 cm-2 sr−1) as a measurement of tumor growth after tumor cell infusion. The y axis indicates the photon flux (p s−1 cm-2 sr−1). (d) Kaplan–Meier survival curves of mice receiving TERT mRNA delivery CAR T cell treatment, CI-TERT mRNA (CI) delivery CAR T cell treatment, untreated CAR T cells treatment or GFP T cells treatment. The survival curves for the indicated TERT mRNA delivery CAR T cell groups were compared using the log-rank test, showing a significantly increased median survival compared with the CAR T group, and when comparisons were made between the TERT-CAR T group and CI-CAR T group, the data exhibited significant difference (P=0.0002, P<0.01) (log-rank test, P<0.01). (e, f) Persistence and proliferation of CAR T cells in vivo. Detection of CAR T cells in the blood of Raji-inoculated NPG/Vst mice every week after T-cell injection using flow cytometry and qPCR. When comparisons were made between the TERT-CAR T group and CI-CAR T group, the data exhibited significant difference in e P=0.0013 (P<0.01), and in f P=0.0117 (P<0.05).
