Related Experiment Video
Updated: Jun 20, 2026
Live Cell Imaging of the TGF- β/Smad3 Signaling Pathway In Vitro and In Vivo Using an Adenovirus Reporter System
Published on: July 30, 2018
A chimeric adenovirus with an Ad 3 fiber knob modification augments glioma virotherapy
Suvobroto Nandi1, Ilya V Ulasov, Cleo E Rolle
1The Brain Tumor Center, The University of Chicago, Chicago, IL, USA.
Background:
Malignant gliomas remain refractory to treatment despite advances in chemotherapy and surgical techniques. Viral vectors developed to treat gliomas have had low transduction capabilities, limiting their use. Gliomas over-express CD46, CD80, and CD86, all of which bind adenovirus serotype 3.
Methods:
To increase the infectivity and replication of oncolytic vectors in malignant brain tumors, we created a conditionally replicating adenovirus, CRAd-Survivin-5/3, which contains a survivin promoter-driving E1A and a chimeric fiber consisting of adenovirus serotype 3 knob.
Results:
In vitro, this modified CRAd showed ten- to 100-fold increased cytotoxicity against glioma cells. Ex vivo analysis of primary glioblastoma multiforme samples infected with CRAd-Survivin-5/3 showed an increase in cytotoxicity of 20-30% compared to adenovirus wild-type (AdWT). In normal human astrocytes and normal brain tissues, CRAd-Survivin-5/3 exhibited 30-40% and 10-15% lower cytotoxicity than AdWT, respectively. In an intracranial xenograft model of glioma, this oncolytic virus increased tumor-free survival and overall lifespan by 50% compared to controls (p < 0.05).
Conclusions:
CRAd-Survivin-5/3 represents an attractive alternative to existing vectors and should be tested further in the pre-clinical setting.
Insights
A novel oncolytic virus, CRAd-Survivin-5/3, shows enhanced killing of glioma cells and increased survival in preclinical models. This modified adenovirus offers a promising new strategy for treating malignant brain tumors.
Area of Science:
- Oncolytic virotherapy
- Gene therapy for brain tumors
Background:
- Malignant gliomas are difficult to treat, with limited success from current therapies.
- Existing viral vectors for glioma treatment have poor transduction efficiency.
- Gliomas overexpress CD46, CD80, and CD86, which are receptors for adenovirus serotype 3.
Purpose of the Study:
- To develop an oncolytic adenovirus with improved infectivity and replication in malignant brain tumors.
- To enhance the efficacy of viral therapy for gliomas.
Main Methods:
- A conditionally replicating adenovirus (CRAd-Survivin-5/3) was engineered.
- The vector incorporates a survivin promoter driving E1A expression.
- A chimeric fiber with adenovirus serotype 3 knob was utilized to target glioma cell receptors.
Main Results:
- CRAd-Survivin-5/3 demonstrated 10-100 fold increased cytotoxicity against glioma cells in vitro.
- Ex vivo studies showed a 20-30% increase in cytotoxicity in glioblastoma samples compared to wild-type adenovirus.
- The modified virus exhibited reduced cytotoxicity in normal astrocytes and brain tissue.
- In a glioma xenograft model, CRAd-Survivin-5/3 significantly improved tumor-free survival and overall lifespan by 50%.
Conclusions:
- CRAd-Survivin-5/3 shows significant potential as an oncolytic vector for malignant gliomas.
- The enhanced infectivity and tumor-specific replication make it a promising candidate for further pre-clinical investigation.
