Combining anti-PD-1/CD137 mAb with cisplatin induced complete remission of established ID8 cancer with long-lasting systemic tumor-specific immunity.

Abstract

<p>Mice (10/group) transplanted i.p. with 3 x 10⁶ ID8 cells 10 days earlier were injected i.p. with two doses of control, anti-PD-1, anti-CD137 or anti-PD-1/CD137 mAb (0.5 mg per dose per mouse) at 4 days interval with or without coadministration of cisplatin (10mg/kg) at the first treatment and their survival was evaluated (A). Mice (10/group) treated with combined anti-PD-1/CD137/cisplatin were depleted of lymphocyte subsets by injection of anti-CD4 (0.2 mg/mouse), anti-CD8 (0.2 mg/mouse), anti-NK1.1 (0.1 mg/mouse) or control mAb (0.2 mg/mouse) 48 and 72 hours prior to the first treatment and every 3-4 days thereafter for the duration of the experiments. Untreated tumor-bearing mice were as negative controls (UNT group). The survival of mice was recorded (B). Fifteen long-term surviving mice (120 days after original transplantation of ID8 cells) pooled from 2 experiments were challenged (5 mice/group) with ID8 cells given i.p. or s.c. or with TC1 cells transplanted s.c. (C); naive mice were transplanted with tumor cells as controls (D) and their survival was recorded. Mice (6/group) with established TC1 tumors of 4-5 mm mean diameter were injected i.p. with two doses of control, anti-PD-1, anti-CD137 or anti-PD-1/CD137 mAb (0.5 mg per dose per mouse) at 4 days interval with or without coadministraation of cisplatin (10 mg/kg) at the first treatment; tumor growth was measured (E) and survival was recorded (F). Data are representative of 2 experiments for <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0084927#pone-0084927-g006" target="_blank">Figure 6A-D</a>.</p