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Updated: Jul 11, 2025
Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Oncolytic virus Ad-TD-nsIL-12 inhibits glioma growth and reprograms the tumor immune microenvironment
Shenglun Li1, Yuduo Guo2, Weihai Ning1
1Department of Neurosurgery, Sanbo Brain Hospital, Capital Medical University, Beijing, China.
Aims:
Gliomas are the most common central nervous system malignancies, with limited therapeutic options and poor prognosis, which are primarily attributed to the "immune desert" microenvironment. Previously, we constructed a three-gene-deleted oncolytic adenovirus (Ad-TD) loaded with non-secreting interleukin-12 (nsIL-12), which could be amplified in tumor cells and induce immunity to suppress tumors. However, the effects of this oncolytic virus on gliomas and their immune microenvironment remain unclear. There is an urgent need for further research.
Materials And Methods:
We constructed a Syrian hamster brain tumor model and demonstrated the efficacy and mechanism of the novel oncolytic virus in treating brain tumors through a series of in vitro and in vivo experiments. We investigated the efficacy and safety (the number of hamsters in each group is either 5 or 10) of the oncolytic virus treatment in Syrian hamsters using a virus-treated group, a control virus-treated group, and a blank control group.
Key Findings:
In vitro assays showed that Ad-TD-nsIL-12 could specifically proliferate in brain tumor cells which induce tumor cell apoptosis and intracellular expression of interleukin (IL)-12. Moreover, in vivo experiments demonstrated that Ad-TD-nsIL-12 could effectively inhibit the progression of brain tumors and prolong survival. Ad-TD-nsIL-12 significantly enhanced T-cell infiltration in the brain tumor microenvironment.
Significance:
Ad-TD-nsIL-12 can inhibit glioma progression and increase T-cell infiltration in the tumor tissue, particularly infiltration by cytotoxic T cells (CD8+). Ad-TD-nsIL-12 can amplify and produce IL-12, inducing anti-glioma immune responses to inhibit tumor progression.
Insights
This study shows that Ad-TD-nsIL-12 effectively suppresses glioma growth and boosts anti-tumor immunity by increasing T-cell infiltration in the brain tumor microenvironment.
Area of Science:
- Oncology
- Immunotherapy
- Virology
Background:
- Gliomas are aggressive brain tumors with poor prognosis, often due to an immunosuppressive tumor microenvironment.
- Limited therapeutic options necessitate novel treatment strategies for gliomas.
Purpose of the Study:
- To evaluate the efficacy and mechanism of a novel oncolytic adenovirus (Ad-TD) engineered to express non-secreting interleukin-12 (nsIL-12) in treating brain tumors.
- To investigate the impact of Ad-TD-nsIL-12 on the glioma immune microenvironment.
Main Methods:
- A Syrian hamster brain tumor model was utilized for in vitro and in vivo assessments.
- Efficacy and safety were evaluated by comparing Ad-TD-nsIL-12 treatment with control groups.
Main Results:
- Ad-TD-nsIL-12 demonstrated specific proliferation in brain tumor cells, inducing apoptosis and IL-12 expression.
- In vivo studies confirmed Ad-TD-nsIL-12's ability to inhibit tumor progression and prolong survival.
- Significant enhancement of T-cell infiltration, including cytotoxic CD8+ T cells, was observed in the tumor microenvironment.
Conclusions:
- Ad-TD-nsIL-12 effectively inhibits glioma progression by inducing anti-glioma immune responses.
- The oncolytic virus amplifies IL-12, promoting T-cell infiltration and anti-tumor immunity.
