Fig. 2: Combination of OVs and IL-18 ligand synergistically enhances the antitumor efficacy. | Nature Communications

Fig. 2: Combination of OVs and IL-18 ligand synergistically enhances the antitumor efficacy.

From: Suppression of multiple mouse models of refractory malignancies by reprogramming IL-18 ligand-receptor interaction

Fig. 2

a−c Female C57BL/6 J or BALB/c mice aged 4−6 weeks were implanted with B16F10 or CT26 cells and treated with PBS or M1 (1.5 × 107 PFU) via tail vein injection for 5 consecutive days. On the day of the first administration of M1, wtIL-18 protein (0.32 mg/kg) and mutIL-18 (0.32 mg/kg) were intraperitoneally injected twice weekly for a total of 5 times. a, b n = 7 mice per group; c, n = 10 mice per group. d Female BALB/c mice aged 4–6 weeks were implanted with CT26 cells and treated with HSV-1 (2 × 106 PFU) via a single intra-tumor injection. On the day of the administration of HSV-1, mutIL-18 (0.32 mg/kg) were intraperitoneally injected twice weekly for a total of 5 times. PBS, n = 3; Other groups, n = 4. e Construction of M1-wtIL-18 and M1-mutIL-18 and expression of wtIL-18 and mutIL-18 by B16F10 cells after infection with 0.001 MOI M1-wtIL-18 or M1-mutIL-18 for 48 h. f Activity of wtIL-18 (4 ng/mL, total 1 ml) and mutIL-18 (4 ng/mL, total 1 ml) expressed by M1-wtIL-18 and M1-mutIL-18 after infecting B16F10 cells. The mutIL-18 protein (4 ng/mL, total 1 ml) expressed by plasmid transformed into prokaryotes was used as a positive control. g Replication kinetics after infection of B16F10 cells with 0.01 MOI M1-wtIL-18 or M1-mutIL-18. e−g n = 3 biological replicates per group. h Cell viability after infection of B16F10 cells with different MOI M1-wtIL-18 or M1-mutIL-18 for 24 h. n = 4 biological replicates per group. i, j, Efficacy of M1-wtIL-18 and M1-mutIL-18 treated as in (a). n = 7 mice per group. k, l Efficacy of UV-inactivated M1-mutIL-18 treated as in (a). n = 5 mice per group. UV, ultraviolet. m, n Efficacy of mutIL-18 protein in combination with M1 and M1-mutIL-18 treated as in (a). n = 7 mice per group. In all figures, data with error bars represent mean ± SD. ns, not significant. *P  <  0.05, **P  <  0.01, ***P  <  0.001, ****P  <  0.0001. P-values were calculated using unpaired, two-tailed Student’s t-test (a−f, i, k, m), two-way ANOVA (g, h) or log rank test (a−c, j, l, n).

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