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. 2022 Jun 17;30(12):3658–3676. doi: 10.1016/j.ymthe.2022.06.010

Figure 4.

Figure 4

Combination therapy with OV-mOX40L/IL12 and TILs led to marked tumor regression in immunocompetent murine tumor models

(A) Schematic of C57BL/6J mice with subcutaneously implanted tumors treated with the OV and TILs. Immunocompetent C57BL/6J mice (n = 7) were implanted subcutaneously with MC38 cells, and the established tumors were intratumorally injected with the indicated OV followed by intratumoral adoptive transfer of the corresponding TILs. Tumor growth was measured every other day. (B) Tumor volumes are shown as the mean ± SEM. (C) The survival curve of MC38 tumor-bearing mice (n = 7) was plotted using the Kaplan-Meier analysis, and the log rank test indicated a significant difference in the survival curves between the OV-mOX40L/IL12, PD-1 antagonist antibody and TIL combination therapy groups and the OV-Δ34.5 + TIL group. NS, not significant, ∗∗∗p < 0.001. Mice that were previously cured of MC38 tumors with the combination therapy and age-matched treatment-naive mice (n = 6) were subcutaneously inoculated with MC38 cells. Tumor growth in individual mice (D) and the survival curve (E) are shown. NS, not significant, ∗∗p < 0.01. (F) Mice were subcutaneously inoculated with MC38 cells in both flanks. After the establishment of tumors, PBS and OV-mOX40L/IL12 were injected into the tumors on one side (treated side) on days 7 and 9. On day 11, mice were intratumorally administered with TILs. Growth of the injected tumors and the distant tumors was measured. Data from each mouse (n = 6 mice per group) are shown. (G) Kaplan-Meier survival curves from the experiment. ∗∗∗p < 0.001. (H) Antibody-mediated immune cell depletion was then performed individually for CD4+ T cells, NK cells, and CD8+ T cells via i.p. injection according to the depicted schedule. (I) Tumor growth was monitored every 3 days using electric calipers to measure the tumor size (n = 4). (J) Kaplan-Meier survival curves from the experiment described in (H). The p value indicates the difference between tumor-bearing mice receiving and not receiving CD4, CD8, or NK depletion antibodies, as determined by using the log rank (Mantel-Cox) test. NS, not significant, ∗∗p < 0.01.