A novel oncolytic herpes simplex virus that synergizes with phosphoinositide 3-kinase/Akt pathway inhibitors to target glioblastoma stem cells.

ABSTRACT:

Purpose

To develop a new oncolytic herpes simplex virus (oHSV) for glioblastoma (GBM) therapy that will be effective in glioblastoma stem cells (GSC), an important and untargeted component of GBM. One approach to enhance oHSV efficacy is by combination with other therapeutic modalities.

Experimental design

MG18L, containing a U(S)3 deletion and an inactivating LacZ insertion in U(L)39, was constructed for the treatment of brain tumors. Safety was evaluated after intracerebral injection in HSV-susceptible mice. The efficacy of MG18L in human GSCs and glioma cell lines in vitro was compared with other oHSVs, alone or in combination with phosphoinositide-3-kinase (PI3K)/Akt inhibitors (LY294002, triciribine, GDC-0941, and BEZ235). Cytotoxic interactions between MG18L and PI3K/A

SUBMITTER: Kanai R 

PROVIDER: S-EPMC3107877 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature