Perturbing DDR signaling enhances cytotoxic effects of local oncolytic virotherapy and modulates the immune environment in glioma
Marilin Koch, Mykola Zdioruk, Michal O. Nowicki, Alec Griffith, Estuardo Aguilar-Córdova, Laura K. Aguilar, Brian W. Guzik, Francesca Barone, Paul P. Tak, Katharina Schregel, Michael S. Hoetker, James A. Lederer, E. Antonio Chiocca, Ghazaleh Tabatabai, Sean Lawler
Abstract
, long-term survival was increased after combination treatment (66.7%) compared with CAN-2409 (50%) and control. In a tumor re-challenge, long-term immunity after combination treatment was not improved. Our results suggest that ATR inhibition could amplify CAN-2409's efficacy in glioblastoma through increased DNA damage while having complex immunological ramifications, warranting further studies to determine the ideal conditions for maximized therapeutic benefit.
Topics & Concepts
BiologyCancer researchImmune systemOncolytic virusGliomaCytotoxic T cellHerpes simplex virusThymidine kinaseImmunologyVirologyVirusIn vitroBiochemistryVirus-based gene therapy researchCAR-T cell therapy researchinterferon and immune responses