Neural stem cells secreting bispecific T cell engager to induce selective antiglioma activity
Katarzyna C. Pituch, Μαρκέλλα Ζαννίκου, Liliana Ilut, Ting Xiao, Michael I. Chastkofsky, Madina Sukhanova, Nicola Bertolino, Daniele Procissi, Christina Amidei, Craig Horbinski, Karen S. Aboody, C. David James, Maciej S. Lesniak, Irina V. Balyasnikova
Abstract
Significance Glioblastoma (GBM) is the most aggressive and lethal brain tumor in adults. The GBM microenvironment is highly immunosuppressive, rendering T cells incapable of recognizing and eliminating malignant cells. We developed bispecific T cell engagers (BiTEs) that successfully engage patients' T cells to attack and kill GBM expressing interleukin 13 receptor alpha 2 (IL13Rα2). Neural stem cells (NSCs) engineered to secrete BiTE migrate readily within the brain tissue to established tumors and produce BiTE protein within the malignant tissue. Treatment of animals bearing IL13Rα2-expressing patient-derived GBM xenografts with therapeutic NSCs resulted in significant survival benefits in mice. These results show an exciting potential of NSCs as a delivery platform for BiTE therapy to improve outcomes for GBM patients.