ArticleNeuro-oncology2024
Targeting IGF2 to reprogram the tumor microenvironment for enhanced viro-immunotherapy.
Article in Neuro-oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03152318 (A Phase I Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2, a Genetically Engineered HSV-1 Virus, and Immunomodulation With Cyclophosphamide), which is not on this map. Cited by 19 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase I Study of the Treatment of Recurrent Malignant Glioma With rQNestin34.5v.2, a Genetically Engineered HSV-1 Virus, and Immunomodulation With Cyclophosphamide
Who cites it
19 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Pooled it
- Selective targeting of glioma via the SCARB2 receptor: transcriptomic, proteomic andFrontiers in cellular and infection microbiology · 2025Pooled it
- Therapy-induced IGF1R signaling as an actionable vulnerability in oncolytic virotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Development and preclinical evaluation of a decoy DLL4-encoding oncolytic HSV-1 for high-grade glioma.Oncogene · 2026Article
- Unraveling the roles of fibroblast activation protein‑positive cancer‑associated fibroblasts in cancer: From mechanisms to therapy (Review).International journal of oncology · 2026Review
- Overcoming IGF1R-mediated resistance to oncolytic HSV1 and radiotherapy via triple combination therapy.Cell death & disease · 2026Article
- Oncolytic viruses and cytokine-based gene therapies reprogram the tumor microenvironment.Nature cancer · 2026Review
- Emerging role of lncRNA TP53TG1 as a tumor regulator and biomarker in human malignancies.Discover oncology · 2026Review
- The Role of Natural Compounds in Bladder Urothelial Carcinoma Treatment.International journal of molecular sciences · 2026Review
- Immunological Biomarkers in Glioblastoma: Targeting T and NK Cells for Enhanced Diagnosis and Prognosis.Biologics : targets & therapy · 2026Review
- Renal-targeted exosomes inhibiting miR-182-5p for treatment of renal ischemia-reperfusion injury.Bioengineering & translational medicine · 2026Article
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Overcoming IGF1R-Mediated Resistance to Oncolytic HSV1 and Radiotherapy via Triple Combination Therapy.Research square · 2025Article
- Resistance to oncolytic virotherapy: Multidimensional mechanisms and therapeutic breakthroughs (Review).International journal of molecular medicine · 2025Review
- Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025Review
- Unveiling the significance of cancer-testis antigens and their implications for immunotherapy in glioma.Discover oncology · 2024Review
- Enhanced interactions within microenvironment accelerates dismal prognosis in HBV-related HCC after TACE.Hepatology communications · 2024Article
- IGF2 supports glioblastoma growth and immune evasion through a combination of tumor cell-intrinsic and -extrinsic mechanisms.Neuro-oncology advancesArticle
- Targeting immune microenvironment-mediated mesenchymal transition in glioblastoma: Molecular mechanisms and translational strategies.Neuro-oncology advancesReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
backgroundThe FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).
methodsRNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.
resultsTranscriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. Moreover, IGF2 expression was significantly upregulated in 10 out of 14 recurrent GBM patients after treatment with oHSV, rQNestin34.5v.2 (71.4%; P = .0020) (ClinicalTrials.gov, NCT03152318). Depletion of IGF2 substantially enhanced oHSV-mediated tumor cell killing in vitro and improved survival of mice bearing BCBM tumors in vivo. To mitigate the oHSV-induced IGF2 in the TME, we constructed a novel oHSV, oHSV-D11mt, secreting a modified IGF2R domain 11 (IGF2RD11mt) that acts as IGF2 decoy receptor. Selective blocking of IGF2 by IGF2RD11mt significantly increased cytotoxicity, reduced oHSV-induced neutrophils/PMN-MDSCs infiltration, and reduced secretion of immune suppressive/proangiogenic cytokines, while increased CD8 + cytotoxic T lymphocytes (CTLs) infiltration, leading to enhanced survival in GBM or BCBM tumor-bearing mice.
conclusionsThis is the first study reporting that oHSV-induced secreted IGF2 exerts a critical role in resistance to oHSV therapy, which can be overcome by oHSV-D11mt as a promising therapeutic advance for enhanced viro-immunotherapy.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.