Fig. 3
Comparison of model predictions with experimental measures of therapeutic response upon tumor re-challenge. a. Comparison of model predictions with experimental measures of tumor volume, IFN γ and TE3/ TR of mice subjected to tumor re-challenge after one cycle of IL-12 and OXP treatment at day 57. The experimental data were acquired for a group of C57BL/6 mice with 5* 105 MC38Luc1 cells inoculated in the liver on day 0 and subjected to one cycle of OXP (on day 9) and Mif-induced IL-12 (started on day 12 and continued 10 days) treatment. To check the immunological protection against cancer cells in treated animals, the cured mice had a tumor re-challenge of 106 MC38Luc1 cells about one month after completion of previous treatment. Experimental measures of tumor volume, IFN γ, and TE3/ TR (crosses, represent average of n = 16) from Figs. 2 - 5 in [6] were compared to the model predictions (blue curve) generated using a genetic algorithm. b - d. The experimental data were acquired for a group of C57BL/6 mice bearing hepatic tumors treated with the HC-Ad/RUmIL-12 vector and received two cycles of Mifepristone (Mif) induction preceded by OXP (5 mg/kg, intraperitoneally). Animals cured from their hepatic tumors were subjected to a subcutaneous challenge with the same tumor cells (MC38Luc1), and received a third cycle of IL-12 and OXP treatment starting on day 103. Experimental measures of tumor volume for individual mice (squares, triangles, and crosses) from Fig. 7 in [6] were compared to the model predictions (blue curve) generated using a genetic algorithm. Model predictions calibrated to tumor volume for responder, partial-responder, and non-responder mice treated with one cycle of combined therapy after tumor re-challenge are shown in panels b, c, d, respectively. Each graph displays a collection of 30 good fits of model predictions against experimental data. The solid blue curve provides the median model prediction of the 30 good fits, and the dashed purple and green curves indicate the 90% upper and lower boundaries in the model predictions of 30 good fits, respectively. Example parameter values of good fits in each panel are included in Table 2