Systemic Delivery of R-123 Controls Lung Metastasis Development in Combination with α-PD1
(A) Schematic of lung metastatic setting. HER2-LLC1 cells were i.v. injected into the mouse tail vein. Treatments started after 3 days (d0): R-123 was i.v. delivered (five injections at 108 PFU each), combined with α-PD1. At day 14 lung nodules were counted. (B) Number of lung nodules in vehicle-treated (black symbols), α-PD1-treated (gray symbols), or R-123/α-PD1-treated (red symbols) mice. Bars show mean with SEM of two independent experiments; dots represent individual animals (n = 10–20). (C) Prime-boost immunization scheme with WT HSV. For the efficacy experiment, naive versus HSV immune mice were i.v. inoculated with HER2-LLC1 cells. Treatments started after 3 days (d0) and were performed as described in (A). (D) Anti-HSV antibody serum titers determined by plaque reduction neutralization test at week 12 after immunization. The y axis indicates the dilution factor at which the number of viral plaques was reduced by 50% compared to the control sample (virus alone). Bars show mean with SEM. (E) Numbers of lung nodules in untreated mice (black dots ) versus treated mice, HSV naive mice (red dots), or HSV immune mice (blue dots) are shown. Bars show mean with SEM; dots represent individual animals (n = 8–12). Statistics were generated using an unpaired Mann-Whitney nonparametric test. ∗p ≤ 0.05, ∗∗∗∗p ≤ 0.001.