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Updated: May 10, 2026
Intranasal Delivery of Therapeutic Stem Cells to Glioblastoma in a Mouse Model
Published on: June 4, 2017
A preclinical evaluation of neural stem cell-based cell carrier for targeted antiglioma oncolytic virotherapy
Atique U Ahmed1, Bart Thaci, Alex L Tobias
1The Brain Tumor Center, University of Chicago, Chicago, IL 60637, USA.
Background:
Oncolytic adenoviral virotherapy (OV) is a highly promising approach for the treatment of glioblastoma multiforme (GBM). In practice, however, the approach is limited by poor viral distribution and spread throughout the tumor mass.
Methods:
To enhance viral delivery, replication, and spread, we used a US Food and Drug Administration-approved neural stem cell line (NSC), HB1.F3.CD, which is currently employed in human clinical trials. HB1.F3.CD cells were loaded with an oncolytic adenovirus, CRAd-Survivin-pk7, and mice bearing various human-derived GBMs were assessed with regard to NSC migration, viral replication, and therapeutic efficacy. Survival curves were evaluated with Kaplan-Meier methods. All statistical tests were two-sided.
Results:
Antiglioma activity of OV-loaded HB1.F3.CD cells was effective against clinically relevant human-derived glioma models as well as a glioma stem cell-enriched xenograft model. Median survival was prolonged by 34% to 50% compared with mice treated with OV alone (GBM43FL model median survival = 19.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.26, 95% confidence interval [CI] = 1.21 to 12.23, P = .02; GBM12 model median survival = 43.5 days, OV alone vs NSC + OV, hazard ratio of survival = 2.53, 95% CI = 1.21 to 10.38, P = .02). OV-loaded HB1.F3.CD cells were shown to effectively migrate to the contralateral hemisphere and hand off the therapeutic payload of OV to targeted glioma cells. In vivo distribution and migratory kinetics of the OV-loaded HB1.F3.CD cells were successfully monitored in real time by magnetic resonance imaging. OV-loaded NSCs retained their differentiation fate and were nontumorigenic in vivo.
Conclusions:
HB1.F3.CD NSCs loaded with CRAd-Survivin-pk7 overcome major limitations of OV in vivo and warrant translation in a phase I human clinical trial for patients with GBM.
Insights
Neural stem cells loaded with oncolytic adenovirus effectively treat glioblastoma in mice by improving viral delivery and spread. This approach enhances survival and warrants clinical trials for brain tumor patients.
Area of Science:
- Oncolytic virotherapy
- Neuro-oncology
- Stem cell therapy
Background:
- Oncolytic adenoviral virotherapy (OV) shows promise for glioblastoma multiforme (GBM) treatment.
- Current limitations include poor viral distribution and tumor spread.
Purpose of the Study:
- To enhance viral delivery, replication, and spread for GBM treatment.
- To evaluate the efficacy of neural stem cells (NSCs) loaded with OV.
Main Methods:
- Used FDA-approved HB1.F3.CD neural stem cells loaded with CRAd-Survivin-pk7 oncolytic adenovirus.
- Assessed NSC migration, viral replication, and therapeutic efficacy in mice with human-derived GBMs.
- Monitored in vivo distribution using real-time magnetic resonance imaging.
Main Results:
- OV-loaded HB1.F3.CD cells demonstrated antiglioma activity in relevant models.
- Median survival increased by 34%–50% compared to OV alone.
- NSCs effectively migrated, delivered the OV payload, and were nontumorigenic.
Conclusions:
- HB1.F3.CD NSCs loaded with CRAd-Survivin-pk7 overcome OV limitations in vivo.
- This approach is suitable for translation into a Phase I clinical trial for GBM patients.
