ArticleNeuro-oncology2018
Preclinical investigation of combined gene-mediated cytotoxic immunotherapy and immune checkpoint blockade in glioblastoma.
Article in Neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
54 citing papers in PubMed.
- Prolonged survival after systemic immune reactivation by aglatimagene besadenovec plus valacyclovir in immune checkpoint inhibitor-refractory non-small cell lung cancer.Journal for immunotherapy of cancer · 2026Trial
- A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- The promise of immunotherapy for central nervous system tumours.Nature reviews. Immunology · 2026Review
- Cellular Allies Against Glioblastoma: Therapeutic Potential of Macrophages and Mesenchymal Stromal Cells.Pharmaceutics · 2026Review
- Expanding the immunotherapeutic toolbox in glioblastoma: A safe and feasible strategy at the point of surgery.Neuro-oncology · 2025Article
- A multi-institutional phase 1 clinical trial exploring upfront multimodal standard of care and combined immunotherapies for newly diagnosed glioblastoma.Neuro-oncology · 2025Article
- Suicide gene therapy targeting ewing sarcoma via an ewing-specific GGAA promoter.Scientific reports · 2025Article
- Oncolytic immunovirotherapy: finding the tumor antigen needle in the antiviral haystack.Immunotherapy · 2025Review
- Dynamic Tracking of Tumor Microenvironment Modulation Using Kaede Photoconvertible Transgenic Mice Unveils New Biological Properties of Viral Immunotherapy.Cancer research communications · 2025Article
- Immunotherapy for glioblastoma: current state, challenges, and future perspectives.Cellular & molecular immunology · 2024Review
- In vivo mouse models for adult brain tumors: Exploring tumorigenesis and advancing immunotherapy development.Neuro-oncology · 2024Review
- Practical immunomodulatory landscape of glioblastoma multiforme (GBM) therapy.Journal of the Egyptian National Cancer Institute · 2024Review
- Immune Checkpoint Inhibitors and Glioblastoma: A Review on Current State and Future Directions.Journal of immunotherapy and precision oncology · 2024Article
- Review
- Opportunities and challenges of combining adoptive cellular therapy with oncolytic virotherapy.Molecular therapy oncolytics · 2023Review
- Updates in Glioblastoma Immunotherapy: An Overview of the Current Clinical and Translational Scenario.Biomedicines · 2023Review
- Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.Molecules (Basel, Switzerland) · 2023Review
- NamiRNA-mediated high expression of KNSTRN correlates with poor prognosis and immune infiltration in hepatocellular carcinoma.Contemporary oncology (Poznan, Poland) · 2023Article
- Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model.Frontiers in immunology · 2023Article
- Uncovering transcriptomic landscape alterations of CAN-2409 inFrontiers in medicine · 2023Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
Background: Combined immunotherapy approaches are promising cancer treatments. We evaluated anti-programmed cell death protein 1 (PD-1) treatment combined with gene-mediated cytotoxic immunotherapy (GMCI) performed by intratumoral injection of a prodrug metabolizing nonreplicating adenovirus (AdV-tk), providing in situ chemotherapy and immune stimulation. Methods: The effects of GMCI on PD ligand 1 (PD-L1) expression in glioblastoma were investigated in vitro and in vivo. The efficacy of the combination was investigated in 2 syngeneic mouse glioblastoma models (GL261 and CT-2A). Immune infiltrates were analyzed by flow cytometry. Results: GMCI upregulated PD-L1 expression in vitro and in vivo. Both GMCI and anti-PD-1 increased intratumoral T-cell infiltration. A higher percentage of long-term survivors was observed in mice treated with combined GMCI/anti-PD-1 relative to single treatments. Long-term survivors were protected from tumor rechallenge, demonstrating durable memory antitumor immunity. GMCI led to elevated interferon gamma positive T cells and a lower proportion of exhausted double positive PD1+TIM+CD8+ T cells. GMCI also increased PD-L1 levels on tumor cells and infiltrating macrophages/microglia. Our data suggest that anti-PD-1 treatment improves the effectiveness of GMCI by overcoming interferon-induced PD-L1-mediated inhibitory signals, and GMCI improves anti-PD-1 efficacy by increasing tumor-infiltrating T-cell activation. Conclusions: Our data show that the GMCI/anti-PD-1 combination is well tolerated and effective in glioblastoma mouse models. These results support evaluation of this combination in glioblastoma patients.
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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.