Fig. 4.
Systemic treatment of preformed GBM xenograft tumors with SVV-001 significantly prolongs survival times. (A) Graphs showing the log-rank analysis of animal survival times. Treatment of preestablished orthotopic xenografts (n = 10 per group) was performed through a single tail vein injection of SVV-001 (5 × 1012vp/kg) after the engrafted tumor cells (1 × 105/mouse) were allowed to grow for 2 and 4 wk, respectively. Mice in the control group (n = 10) received the injection of PBS that was used to resuspend SVV-001. (B) All pairwise multiple comparison procedures were performed with the Holm–Sidak method to isolate the group or groups that differ from the others. (C) Representative images showing the elimination of ICb-1227AA xenografts by SVV-001. In the untreated animals (#3060 and #3061), the growth of xenograft tumors (arrows) almost completely destroyed the mouse cerebellum and caused severe hydrocephalus, as evidenced by enlarged bilateral ventricles (*). In the 2 mice that were treated with SVV-001 4 wk (#3079) and 2 wk (#3068) post tumor injection, respectively, no remnant of human tumor cells were detected with IHC staining using human-specific monoclonal antibodies against mitochondria, although disturbances of granular layer caused by surgical procedure were visible (arrow) compared with normal brain. (D) Western hybridization showing the decreased content of α2,6-linked (top panel) α2,3-linked (middle panel) sialic acids in the resistant model IC-1128GBM (1128) compared with the 5 permissiveness models (++ to +) toward SVV-001 in vivo and/or in vitro. Biotinylated lectins SNL (for α2,6-linkage) and MAL (for α2,3-linkage) were applied to proteins extracted from the xenograft tumors. Arrows indicate the bands that were missing or significantly reduced in the resistant model (IC-1128GBM).