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Published on: November 24, 2014
Oncolytic adenovirus: preclinical and clinical studies in patients with human malignant gliomas
Hong Jiang1, Candelaria Gomez-Manzano, Frederick F Lang
1Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, Texas, USA. hjiang@mdanderson.org
Abstract:
Oncolytic adenoviruses are emerging as a promising alternative therapy for glioma patients and are currently being tested in clinic. In this review, we summarize our experience with gene-based therapy targeting RB pathway in gliomas. Our study has evolved from the development of RB-expressing adenoviral vectors to the characterization of the oncolytic effects on gliomas of the replication competent adenoviruses Delta-24, Delta-24-RGD and ICOVIR. We also review the successful combination of the viruses with chemotherapies that are routinely used in glioma patients, the efficacy of Delta-24-RGD against brain tumor stem cells, the newly described adenovirus-induced autophagy and the potential for the systemic delivery of the oncolytic viruses with human mesenchymal stem cells. Finally, we comment on the preclinical and clinical studies of p53 expressing adenoviral vector and the lessons learned from the experience of Onyx-015, the first oncolytic adenovirus tested in clinical setting.
Insights
Oncolytic adenoviruses show promise for glioma treatment. This review details gene-based therapies targeting the RB pathway, including specific oncolytic viruses and their combination with chemotherapy.
Area of Science:
- Oncology
- Virology
- Gene Therapy
Background:
- Gliomas are aggressive brain tumors with limited treatment options.
- Oncolytic adenoviruses represent a novel therapeutic strategy for glioma.
- Targeting the Retinoblastoma (RB) pathway is a key focus in glioma gene therapy.
Purpose of the Study:
- To review gene-based therapies for gliomas, focusing on RB pathway targeting.
- To summarize experience with oncolytic adenoviruses, including Delta-24, Delta-24-RGD, and ICOVIR.
- To discuss combinations, stem cell efficacy, and delivery methods for oncolytic adenoviruses.
Main Methods:
- Development and characterization of RB-expressing adenoviral vectors.
- Evaluation of oncolytic effects of replication-competent adenoviruses (Delta-24, Delta-24-RGD, ICOVIR).
- Review of combination therapies, stem cell efficacy, and delivery systems.
Main Results:
- Oncolytic adenoviruses demonstrate efficacy against gliomas.
- Combination with chemotherapy enhances therapeutic effects.
- Delta-24-RGD shows efficacy against brain tumor stem cells.
- Adenovirus-induced autophagy and systemic delivery methods are explored.
Conclusions:
- Oncolytic adenoviruses are a promising therapeutic approach for gliomas.
- Gene-based therapies targeting the RB pathway offer significant potential.
- Further research and clinical trials are warranted for optimizing oncolytic adenovirus therapy.

