Extended Data Fig. 5: Therapeutic efficacy of LNP-Rep encoding IL-12 in distinct treatment models.
a,b, Groups of C57Bl/6 mice (n=10/group) bearing established B16F10 tumors were treated when tumors reached 50 mm2 with a single injection of 10 µg LNP-rep(IL-12-alb-lum) on day 7 (indicated by red arrows) or with 2.3 µg recombinant IL-12-alb-lum on days 5, 11, and 17 (indicated by blue arrows). Shown are average (mean + s.d.) tumor growth (a) and overall survival (b) over time. c,d, Groups of Balb/c mice bearing established CT26 tumors were treated when tumors reached 50 mm2 with a single injection on day 7 or 3 injections (day 7, 10, 13) of 10 µg LNP-rep(IL-12-alb-lum) starting from day 7 (untreated n=6 mice/group, other groups n=8 mice/group). Shown are average (mean + s.e.m.) tumor growth (c) and overall survival (d) over time. e–g, Groups of C57Bl/6 mice bearing established B16F10 tumors were treated when tumors reached 50 mm2 with a single injection of different dosages of the LNP-encapsulated replicon RNA as indicated. Shown are IL-12 levels (mean + s.e.m.) in tumors at one day post injection as measured by ELISA (n=5 mice/group (e), average (mean + s.d.) tumor growth (f) and overall survival (g) over time with the treatments as indicated (untreated n=6 mice/group, other groups n=8 mice/group). n.d., non-detectable. h–j, C57Bl/6 mice (untreated n=12 mice/group, other groups n=14 mice/group) were inoculated s.c. with 106 and 0.3x106 B16F10 cells in the left and right flanks, respectively. When the left flank tumor reached ~50 mm2 in size, this lesion was injected with 10 µg of the indicated LNP-replicon. Shown is tumor area (mean + s.d.) in each flank (h, i), and mice survival over time (j). P values were determined by one-sided Turkey’s multiple comparison test (Fig. 5f, h, i), or by one-sided Log-Rank (Mantel-Cox) test (Fig. 5b, d, g, j) using PRISM Software and exact P values were indicated.
