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. Author manuscript; available in PMC: 2022 Jun 1.
Published in final edited form as: Mol Cancer Ther. 2021 Sep 22;20(12):2469–2482. doi: 10.1158/1535-7163.MCT-20-0144

Figure 6. Combinatorial IGF-Trap/anti PD-1 therapy further decreases the number of liver metastases and prolongs survival.

Figure 6.

Experimental liver metastases were generated by the inoculation of 1x105 (for males, A-E), and 5x105 (for females, F-J) LMP cells via the intrasplenic/portal route. Treatment with 5 mg/kg IGF-Trap (or PBS) i.v. was initiated 1 day post tumor inoculation and continued twice weekly for a total of 5 injections per mouse. Treatment with 10 mg/kg PD-1 or the IgG isotype control was administered i.p. on alternate days for a total of 5 injections per mouse (see supplementary Fig. 6). A total of 9–10 male mice and 9–12 female mice were injected per treatment group. Mice were sacrificed on day 21 and visible liver metastases enumerated without prior fixation. Results are based on 2 experiments each, for male and female mice. Shown in (A&F) are the numbers of metastases counted per liver and in (B&G) the mean diameters of the visible metastases per liver. There were no significant differences in either the numbers or sizes of metastases between untreated mice and mice treated with the IgG isotype control. Shown in (C&H) are representative livers from each group where arrows denote metastases. Shown in (D&I) are representative images of H&E stained FFPE liver sections where metastases are encircled and in (E&J) the means of total tumor surface area per section (±SEM) expressed as % of total liver surface area and based on analysis of 9 sections per group (Scale bar – 100 μM). *p ≤ 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; NS-not significant. To test the effect of the combinatorial therapy on survival, syngeneic B6.129 F1 female mice were injected via the intrasplenic/portal route with 1x105 LMP tumor cells (5 mice per group) and treatment with 5 mg/kg IGF-Trap (or vehicle) i.v. was initiated 1 day post tumor inoculation and continued twice weekly. Treatment with 10 mg/kg anti PD-1 antibody i.p was administered on alternate days. The treatments continued for a total of 5 weeks or until animals were moribund and euthanized. Shown in (K) is a Kaplan Meier plot for each of the treatment groups. *p< 0.05 as assessed by the Gehan-Breslow-Wilcoxon Test.