Omics · study · 2026
IDH1-R132H Enhances Oncolytic HSV-1 Therapy by Facilitating Viral Entry and Immune Activation in Glioma
Listed in NCBI GEO
Oncolytic virotherapy represents a promising yet under-explored approach for precision cancer treatment, particularly when tailored to tumor-specific molecular profiles.
Description
Patients with high-grade isocitrate dehydrogenase (IDH) mutant astrocytomas have limited treatment options and experience poor prognoses. Here, we investigate the therapeutic potential of rQNestin34.5v.2 (CAN-3110), an engineered oncolytic herpes simplex virus 1 (oHSV-1), in the context of IDH1-R132H-mutant high-grade diffuse gliomas.
We demonstrate that the IDH1-R132H mutation increases glioma susceptibility to viral infection through upregulation of Nectin 1, the main cellular entry receptor for HSV-1 found in gliomas. Concurrently, IDH1-R132H-driven DNA hypermethylation suppresses interferon (IFN) signaling, an essential antiviral pathway, contributing to a permissive tumor microenvironment that facilitates viral replication and increases tumor cell susceptibility to virus-induced apoptosis.
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In immunocompetent IDH1-R132H murine glioma models, intratumoral administration of rQNestin34.5v.2 elicits robust immune activation, characterized by increased immune cell infiltration into the tumor and systemic IFN-γ release. However, elevated expression of poliovirus receptor (PVR or CD155) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating lymphocytes suggested a potential resistance mechanism to virotherapy.
Combining rQNestin34.5v.2 with TIGIT blockade enhanced therapeutic efficacy and improved survival outcomes compared to monotherapy. These data show that IDH1-R132H modulates viral entry and immune evasion, identifying it as a predictive biomarker for oncolytic virotherapy response.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301461 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301461 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1285277 ncbi.nlm.nih.gov/bioproject/PRJNA1285277 ↗
project · from NCBI GEO
- PubMed 42310302 pubmed.ncbi.nlm.nih.gov/42310302 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 75%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE301461 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |