Myxoma Virus Infection Promotes NK Lysis of Malignant Gliomas In Vitro and In Vivo
Figure 9
M153R mediates enhanced NK cell-mediated clearance of U87 tumor with prolonged survival.
(A) Survival study to compare oncolytic capacity of MYXV with vMyx-M153KO. Dead virus (DV) was used as control. CB-17 SCID mice with established tumors were treated with either DV (n = 4) or MYXV (5×106 ffu/ml, n = 5) or vMyx-M153KO (5×106 ffu/ml, n = 5) on day 19 post tumor implantation. Log-rank P1 (.0110) represents MYXV vs. DV, log-rank P2 (.0250) represents vMyx-M153KO vs. DV, log-rank P3 (.9003) represents MYXV vs. vMyx-M153KO. (B) A heat map indicating tumor size in 5 to 6 mice in each group is shown. CB-17 SCID mice with established tumors were treated with either NK or a combination of MYXV+NK or vMyx-M153KO+NK. NK cells (1.5×105 NK cells) were administered intratumorally, 48 h (day 16 post tumor implantation) following intratumoral MYXV (5×106 ffu/ml) or vMyx-M153KO (5×106 ffu/ml) treatment (day 14 post tumor implantation). Images show accelerated NK clearance in MYXV+NK-treated group compared with NK or vMyx-M153KO+NK-treated group. (C) Survival curves showing that mice treated with MYXV+NK survived longer than NK-treated mice (HR = 31.26, 95% CI of HR = 4.097 to 238.5, log-rank P1 = .0009) and vMyx-M153KO+NK-treated mice (HR = 0.05532, 95% CI of HR = 0.006701 to 0.4567, log-rank P2 = .0072).