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Updated: Dec 23, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Enterovirus A71 Oncolysis of Malignant Gliomas
Xiaowei Zhang1, Hanzhong Wang2, Yuhan Sun3
1State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, China.
Abstract:
Malignant gliomas, the most lethal type of primary brain tumor, continue to be a major therapeutic challenge. Here, we found that enterovirus A71 (EV-A71) can be developed as a novel oncolytic agent against malignant gliomas. EV-A71 preferentially infected and killed malignant glioma cells relative to normal glial cells. The virus receptor human scavenger receptor class B, member 2 (SCARB2), and phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)-mediated cell death were involved in EV-A71-induced oncolysis. In mice with implanted subcutaneous gliomas, intraneoplastic inoculation of EV-A71 caused significant tumor growth inhibition. Furthermore, in mice bearing intracranial orthotopic gliomas, intraneoplastic inoculation of EV-A71 substantially prolonged survival. By insertion of brain-specific microRNA-124 (miR124) response elements into the viral genome, we improved the tumor specificity of EV-A71 oncolytic therapy by reducing its neurotoxicity while maintaining its replication potential and oncolytic capacity in gliomas. Our study reveals that EV-A71 is a potent oncolytic agent against malignant gliomas and may have a role in treating this tumor in the clinical setting.
Insights
Enterovirus A71 (EV-A71) shows promise as an oncolytic agent against malignant gliomas. This virus selectively targets and destroys glioma cells, offering a potential new treatment strategy for brain tumors.
Area of Science:
- Virology
- Neuro-oncology
- Oncolytic Virotherapy
Background:
- Malignant gliomas are aggressive primary brain tumors with limited therapeutic options.
- Developing novel therapeutic strategies, including oncolytic virotherapy, is crucial for improving patient outcomes.
Purpose of the Study:
- To investigate the potential of enterovirus A71 (EV-A71) as an oncolytic agent against malignant gliomas.
- To explore the mechanisms underlying EV-A71-mediated oncolysis and enhance its therapeutic specificity.
Main Methods:
- In vitro studies assessing EV-A71's infectivity and cytotoxicity in glioma and normal glial cells.
- In vivo studies using murine models with subcutaneous and intracranial gliomas to evaluate tumor growth inhibition and survival.
- Genetic modification of the EV-A71 genome with microRNA-124 (miR124) response elements to enhance tumor specificity.
Main Results:
- EV-A71 demonstrated preferential infection and killing of malignant glioma cells over normal glial cells.
- Intratumoral inoculation of EV-A71 significantly inhibited glioma growth in subcutaneous models and prolonged survival in orthotopic intracranial models.
- Engineered EV-A71 with miR124 elements reduced neurotoxicity while preserving oncolytic efficacy against gliomas.
Conclusions:
- EV-A71 is a potent oncolytic agent effective against malignant gliomas.
- EV-A71 exhibits tumor-selective activity, mediated by SCARB2 and PMAIP1 pathways.
- Enhancing EV-A71's tumor specificity through genetic modification holds promise for clinical application in glioma treatment.
