Figure 7. IL-12 partial agonists support MC-38 anti-tumor response without inducing IL-12 associated toxicity.
(A) Schematic of experimental design. Mice were implanted with 5×105 MC-38 cells in Matrigel on day 0. Beginning on day 7, mice were administered daily injections of PBS (n=10), 1μg IL-12 (n=10), 30μg IL-12 (n=9), 30μg 2xAla (n=9), or 30μg 3xAla (n=10) as indicated.
(B) IL-12, but not partial agonists, induces weight loss in tumor-bearing mice. Body weights were normalized to day 7 prior to cytokine treatment. Mice administered 30μg dose of IL-12 succumbed to cytokine toxicity between days 13 and 15.
(C) IL-12, but not partial agonists, enhances systemic IFNγ. Serum IFNγ ELISA on day 10, n=5mice/group.
(D) IL-12, but not partial agonists, reduce mobility. Cumulative displacement of MC-38 bearing mice following cytokine treatment. Quantitation of 30 second videos captured on day 16. Cumulative displacement was calculated as the sum of ΔX and ΔY over time. Data are shown as mean ± standard deviation of n=5 mice/group.
(E) Traces showing XY position of mice in a 30 second video.
(F) IL-12 and partial agonists attenuate MC-38 tumor growth. Tumor volumes were compared on day 20 by Kruskal-Wallis test with Dunn’s multiple comparisons.
(G) IL-12 and partial agonists extend survival of MC-38 bearing mice. Kaplan-Meier curves of mice treated with PBS or IL-12 variants. P values from log-rank test were corrected for multiple comparisons using the Holm-Šídák method.
(H) Individual tumor growth curves of MC-38 bearing mice. Growth curves for PBS-treated mice are shown in gray for comparison with cytokine-treated mice in color.
Data are expressed as mean ± standard deviation and are representative of two independent experiments.