FIG 3.
Combining rNDVs expressing immunocytokines with checkpoint inhibitor induces an antitumor response in a bilateral-flank tumor model. (A) Mouse treatment scheme. Two hundred thousand and 100,000 B16-F10 melanoma cells were implanted in the right and left flanks of C57BL/6 mice 4 days apart. Nine days postimplantation, the tumors were treated with five intratumoral administrations of various rNDVs at 106 PFU every 2 days and three i.p. injections of anti-PD1 (200 μg) or anti-CTLA4 (100 μg) every 4 days. Tumor volumes were measured until day 60. (B and C) Individual tumor volume progressions for the treated tumor (B) and the nontreated tumor (C), along with the CR percentages, for the rNDV–anti-CD28 and rNDV–anti-CD28–mIL-12 treatment cohorts. (D) Overall survival percentages for the different treatment cohorts. The data for survival were analyzed by log rank (Mantel-Cox) tests. The data represent cumulative results from 2 experiments with 8 to 20 mice per group. **, P < 0.01; ***, P < 0.001.