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Updated: Jul 13, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Double-modified oncolytic adenovirus armed with a recombinant interferon-like gene enhanced abscopal effects against
Shan Jiang1,2,3,4, Hui-Hui Chai1,2,3,4, Xian-Long Fang5
1National Center for Neurological Disorders, Shanghai, China.
Background:
The development of new therapies for malignant gliomas has been stagnant for decades. Through the promising outcomes in clinical trials of oncolytic virotherapy, there is now a glimmer of hope in addressing this situation. To further enhance the antitumor immune response of oncolytic viruses, we have equipped a modified oncolytic adenovirus (oAds) with a recombinant interferon-like gene (YSCH-01) and conducted a comprehensive evaluation of the safety and efficacy of this modification compared to existing treatments.
Methods:
To assess the safety of YSCH-01, we administered the oAds intracranially to Syrian hamsters, which are susceptible to adenovirus. The efficacy of YSCH-01 in targeting glioma was evaluated through in vitro and in vivo experiments utilizing various human glioma cell lines. Furthermore, we employed a patient-derived xenograft model of recurrent glioblastoma to test the effectiveness of YSCH-01 against temozolomide.
Results:
By modifying the E1A and adding survivin promoter, the oAds have demonstrated remarkable safety and an impressive ability to selectively target tumor cells. In animal models, YSCH-01 exhibited potent therapeutic efficacy, particularly in terms of its distant effects. Additionally, YSCH-01 remains effective in inhibiting the recurrent GBM patient-derived xenograft model.
Conclusions:
Our initial findings confirm that a double-modified oncolytic adenovirus armed with a recombinant interferon-like gene is both safe and effective in the treatment of malignant glioma. Furthermore, when utilized in combination with a targeted therapy gene strategy, these oAds exhibit a more profound effect in tumor therapy and an enhanced ability to inhibit tumor growth at remote sites.
Insights
A novel oncolytic adenovirus (oAds) modified with a recombinant interferon-like gene (YSCH-01) shows promise for treating malignant gliomas. This enhanced oncolytic virotherapy demonstrates safety and efficacy, including remote tumor inhibition.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Malignant glioma treatment
Background:
- Malignant glioma therapies have seen limited progress for decades.
- Oncolytic virotherapy offers a promising new avenue for treating these aggressive brain tumors.
- Enhancing the antitumor immune response of oncolytic viruses is crucial for improving efficacy.
Purpose of the Study:
- To evaluate the safety and efficacy of a modified oncolytic adenovirus (oAds) equipped with a recombinant interferon-like gene (YSCH-01).
- To compare the therapeutic potential of YSCH-01 against existing treatments for malignant glioma.
- To investigate the ability of YSCH-01 to enhance antitumor immune responses and inhibit tumor growth.
Main Methods:
- Intracranial administration of oAds in Syrian hamsters to assess safety.
- In vitro and in vivo experiments using human glioma cell lines to evaluate YSCH-01 efficacy.
- Utilized a patient-derived xenograft model of recurrent glioblastoma to test YSCH-01 against temozolomide.
Main Results:
- Modified oAds demonstrated significant safety and selective tumor cell targeting.
- YSCH-01 exhibited potent therapeutic efficacy in animal models, including significant distant effects.
- YSCH-01 effectively inhibited tumor growth in a patient-derived xenograft model of recurrent glioblastoma.
Conclusions:
- A double-modified oncolytic adenovirus (YSCH-01) is safe and effective for treating malignant glioma.
- Combination therapy with YSCH-01 and targeted gene strategies enhances antitumor effects.
- This enhanced oncolytic virotherapy demonstrates improved inhibition of tumor growth at remote sites.
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