Therapeutic effect of neural stem cells expressing TRAIL and bortezomib in mice with glioma xenografts

Treatment of glioblastoma remains a challenge in neuro-oncology. We investigated if treatment with neural stem cells engineered to express membrane-bound TRAIL (NSCs-mTRAIL) alone or in combination with proteasome inhibitors is a feasible therapeutic approach for experimental glioma. Glioma cells showed resistance to soluble TRAIL and proteasome inhibitors alone, but responded well to their combined treatment. In co-culture with NSCs-mTRAIL, glioma cells appeared to be more prone to apoptosis than to treatment with soluble TRAIL, which was enhanced by proteasome inhibitor bortezomib. In vivo, the survival of animals bearing intracranial glial xenografts was significantly improved by NSCs-mTRAIL. The addition of bortezomib further enhanced the efficacy of NSCs-TRAIL treated group in one of examined tumor models. These data demonstrate that therapy with NSCs-mTRAIL is a potent cell based approach for treatment of glioma. Such an approach warrants further search for therapeutics capable of increasing sensitivity of glioma cells to mTRAIL in vivo.

► NSCs engineered to express membrane-bound TRAIL induced apoptosis in glioma cells.
► Bortezomib enhanced response of glioma cells to NSCs expressing TRAIL.
► TRAIL expressed on the cell surface of NSCs is a more potent reagent than soluble TRAIL.
► Bortezomib upregulated expression of DR5 in glioma cells in vitro but not in vivo.
► Survival of animals with intracranial glioma was improved in combined treatment.