Fig. 3

Immunostimulatory oncolytic virotherapy in the brainstem demonstrates both inflammatory toxicity and anti-tumor efficacy. (a) GL261 cells were infected in vitro with VV-GMCSF or reovirus (MOI 10). Cell survival (left y-axis, solid bar) or viral titers (right y-axis, dashed bar). (b) Kaplan-Meier survival curve for mice receiving VV-GMCSF/GL261, Reo/GL261, or PBS/GL261 co-implantation. (n = 9 mice/group) Figure is representative of two independent experiments. (c) Representative mouse euthanized for neurologic symptoms four days after VV-GMCSF and tumor co-implantation. H&E image (left, 10x); midbrain (Mid) and medulla (Med), with black arrowhead to indicate inset meningeal infiltrate (vaccinia antigen, red, 40x, middle; CD11b, red, 40x, right). (d) Kaplan-Meier survival curve for 10-day established GL261 tumors treated intratumorally with escalating doses of reovirus. (n = 9 mice/group) Figure is representative of three independent experiments. (e) Representative mice euthanized seven days after reovirus or PBS treatment for histologic analysis. H&E image (left, 20x) and anti-CD3 (red)/DAPI (blue) (right, 40x). (f) Kaplan-Meier survival curve for 10-day established GL261 tumors treated with reovirus (2.5E6 pfu) or PBS, followed by anti-CTLA4/anti-PD1 therapy. (n = 5–6 mice/group) Figure is representative of two independent experiments