Figure 4.

YST-OVH potentiates antitumor efficacy and enhances CD8⁺ T cell activation. (A) Treatment scheme for an orthotopic tumor model. An orthotopic tumor model was established by intrahepatic injection of mouse Hepa1-6-luc cells (expressing luciferase) into immunocompetent PD-1-HU mice. Four days later, the mice were intravenous injected with a saline vehicle control or 3×10⁷ PFU of OVH or YST-OVH. The indicated treatments were taken 4, 7, 9 and 11 days post-tumor implantation. (B) Luciferase fluorescent signals were recorded 1, 2, 3, 4 and 5 weeks after the indicated treatments. (C) Survival of Hepa1-6-luc tumor-bearing mice. (D) Luciferase imaging of mice was performed 1, 2, 3, 4 and 5 weeks after the indicated treatments. (E) Treatment scheme for bilateral flank Hepa1-6 tumor-bearing PD-1-HU mice. Mice bearing tumors received vehicle, OVH or YST-OVH therapy. The tumor growth of injected tumors (F) and distant tumors (G) are shown. (H) Mice bearing Hepa1-6 tumors were intratumorally injected with vehicle, OVH or YST-OVH, and the tumors were collected on day 16 after virus injection and analyzed by flow cytometry. (I) The percentages of tumor-infiltrating IFN-γ⁺, IFN-γ⁺TNF-α⁺, and GZMB⁺CD8⁺ T cells in the tumor CD8⁺ T cell population. Data represent results from one of three (A, E, H) independent experiments with n=6 to n=10 per group. Data for survival were analyzed by the log-rank (Mantel-Cox) test (C). All values are presented as the mean±SEM; repeated-measure ANOVA (F, G) or unpaired two-tailed Student’s t-test (I). *p<0.05; **p<0.01; ***p<0.001. OVH, oncolytic herpes simplex virus-1; YST-OVH, oncolytic herpes simplex virus-1 expressing PD-1 inhibitors; ANOVA, analysis of variance; PFU, plaque-forming units.