Therapeutic concentrations of anti-epileptic drugs do not inhibit the activity of the oncolytic adenovirus Delta24-RGD in malignant glioma.

摘要: Background The oncolytic adenovirus Delta24-RGD is currently being tested inphase I trials for thetreatmentofglioblastoma (GBM).Literaturesuggests that frequently prescribed anticonvulsants these patients, phenytoin (PHE), valproic acid (VPA) and levetiracetam (LEV), may interfere with cellular mechanisms of cancer or virus activity. We therefore investigated the direct effects drugs on infection Methods PHE, VPA, LEV were combined treatment in established glioma cell lines as well a panel patient-derived GBM cultures. Effects efficiency assessed using luciferase-encoding adenoviral vectors. Oncolytic activity was determined by WST-1 assay viral progeny production quantified dilution titration. Results IC50 values anti-epileptic four far above clinically-relevant concentrations. At therapeutic concentrations, anti-epileptics generally did not alter RGD-modified adenovirus, nor affect Delta24-RGD. only exception found U373 cells, where VPA slightly antagonised effect (from 29% to 55% viability, p<0.01) (60% decrease, p<0.01). Oncolysis inhibited any cultures (n=6). In fact, one culture slight enhancement oncolysis PHE found, from 89.7% viability 76% 62.4%, respectively (p<0.01) Conclusions Therapeutic levels acid, do negatively cells. Therefore, there no indication choice anticonvulsantfor seizure control patients should taketreatment into account. Copyright © 2013 John Wiley & Sons, Ltd.