{
  "abstract": "Background Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and limited treatment options. Oncolytic virus (OV) therapy holds promise but is hindered by immune neutralization and poor tumor infiltration. Neural stem cells (NSCs) can enhance OV delivery, and intracerebroventricular (ICV) administration offers broader tumor access. This study evaluates NSC-OV therapy via ICV injection for improved tumor targeting and immune modulation in GBM.Methods NSCs were infected with OV and assessed for viral uptake and replication. In vitro assays examined NSC-OV effects on glioma proliferation and migration. In vivo xenograft and orthotopic models evaluated tumor targeting, therapeutic efficacy, and immune modulation. Humanized immune system mouse models enabled single-cell RNA sequencing and flow cytometry analysis of immune responses.Results NSCs retained their stemness after OV infection. NSCs-OV significantly inhibited glioma cell migration, proliferation, and colony formation in vitro. In orthotopic GBM models, NSCs-OV exhibited enhanced tumor homing, prolonged viral persistence, and reduced tumor burden while minimizing inflammation and systemic toxicity. NSCs protected OV from neutralizing antibodies, leading to sustained efficacy. Single-cell RNA sequencing indicated that NSCs-OV therapy reduced tumor-promoting inflammation by downregulating S100A8/A9, markers of myeloid-derived suppressor cells (MDSCs) and chemotactic factors that recruited MDSCs into tumors. Combining NSCs-OV with Paquinimod further suppressed tumor growth by reducing MDSCs and increasing activated T cells.Conclusions NSCs serve as efficient OV carriers, enhancing tumor targeting, suppressing GBM progression, and modulating the immune landscape. The combination with Paquinimod amplifies therapeutic benefits, offering a promising strategy for improving GBM treatment outcomes.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Huihui Chai"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China"
      ],
      "name": "Houshi Xu"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Shan Jiang"
    },
    {
      "affiliations": [
        "Academician Expert Workstation of Fengxian District, Shanghai Yuansong Biotechnology Limited Company, Shang Hai, China"
      ],
      "name": "Tingting Zhang"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Jiawen Chen"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Ruize Zhu"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, China"
      ],
      "name": "Yue Wang"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Maoyuan Sun"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Beining Liu"
    },
    {
      "affiliations": [
        "Department of Medical, Shanghai Anji Xiekang Biotechnology Company Limited, Shang Hai, China"
      ],
      "name": "Xiaoming Wang"
    },
    {
      "affiliations": [
        "Department of Medical, Shanghai Anji Xiekang Biotechnology Company Limited, Shang Hai, China"
      ],
      "name": "Xicai Sun"
    },
    {
      "affiliations": [
        "Academician Expert Workstation of Fengxian District, Shanghai Yuansong Biotechnology Limited Company, Shang Hai, China",
        "Institute of Smart Biomedical Materials, Zhejiang Sci-Tech University, Hangzhou, Zhejiang, China"
      ],
      "name": "Kangjian Zhang"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Liangfu Zhou"
    },
    {
      "affiliations": [
        "Department of Neurosurgery, Fudan University Huashan Hospital, Shang Hai, China",
        "National Center for Neurological Disorders, Shang Hai, China",
        "Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shang Hai, China",
        "Neurosurgical Institute of Fudan University, Shang Hai, China",
        "Shanghai Clinical Medical Center of Neurosurgery, Shang Hai, China",
        "Shanghai Institute of Microsystem and Information Technology, Shang Hai, China"
      ],
      "name": "Zhi-Feng Shi"
    }
  ],
  "title": "Neural stem cell-delivered oncolytic virus via intracerebroventricular administration enhances glioblastoma therapy and immune modulation",
  "uid": "3df3d464-3b93-585e-8f17-dece6843d885"
}