Fig. 3.

In vivo infection of SVV-001 in the orthotopic xenograft tumors of pediatric GBM. Mice bearing relatively large intracerebral xenografts (8–10 wk post tumor cell transplantation) received a single tail vein injection of SVV-001 (5 × 10¹²vp/kg), after which whole brains were removed at predetermined time points (24 h to 7 days), followed by IHC staining using antibodies specific to the capsid proteins of SVV-001. (A) Representative images showing the time-course increase of positively infected xenograft cells (circled in red) in the permissive model IC-1406GBM (1406, a–d), as contrast to the isolated positive reactions (arrow) in the resistant model IC-1128GBM (1128, e–h). (B) IHC staining of SVV-001 capsid protein in 2 additional permissive models, ICb-1227AA (1227, i–k) and IC-1621GBM (1621, l–m), 96 h post virus injection. The “border” between tumor mass and normal mouse brain in ICb-1277AA is marked by dotted lines (i and j). SVV-001–infected tumor cells both in the core area (i, l–m) and in the invasive front (i–k), including the single invasive cells (j and k, arrow); while sparing the normal mouse granular neurons that are in close proximity with the tumor cells in ICb-1227AA (j, green arrowhead). No SVV-001 positivity was detected in the left ventricle (*) and normal cerebral tissue (n) despite strong positive reaction in tumor cells (l–m) in the same mouse brain of IC-1621GBM. Red arrows in j and k also mark the direction of tumor cell migration. Magnification: ×40 (a–h, j, k, m), ×20 (i, l, n).