Combining the constitutive TRAIL-secreting induced neural stem cell therapy with the novel anti-cancer drug TR-107 in glioblastoma

Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen...

Full description

Saved in:
Bibliographic Details
Published in:Molecular Therapy: Oncology 2024-09, Vol.32 (3), p.200834, Article 200834
Main Authors: Thang, Morrent, Mellows, Clara, Kass, Lauren E, Daglish, Sabrina, Fennell, Emily M J, Mann, Breanna E, Mercer-Smith, Alison R, Valdivia, Alain, Graves, Lee M, Hingtgen, Shawn D
Format: Article
Language:English
Subjects:
apoptosis
glioblastoma
MT: Regular Issue
Original
TNF-related apoptosis inducing ligand
TRAIL
TRAIL resistance
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Tumor-homing neural stem cell (NSC) therapy is emerging as a promising treatment for aggressive cancers of the brain. Despite their success, developing tumor-homing NSC therapy therapies that maintain durable tumor suppression remains a challenge. Herein, we report a synergistic combination regimen where the novel small molecule TR-107 augments NSC-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) therapy (hiNeuroS-TRAIL) in models of the incurable brain cancer glioblastoma (GBM) . We report that the combination of hiNeuroS-TRAIL and TR-107 synergistically upregulated caspase markers and restored sensitivity to the intrinsic apoptotic pathway by significantly downregulating inhibitory pathways associated with chemoresistance and radioresistance in the TRAIL-resistant LN229 cell line. This combination also showed robust tumor suppression and enhanced survival of mice bearing human xenografts of both solid and invasive GBMs. These findings elucidate a novel combination regimen and suggest that the combination of these clinically relevant agents may represent a new therapeutic option with increased efficacy for patients with GBM.
ISSN:2950-3299
2950-3299
DOI:10.1016/j.omton.2024.200834