Evidence map›Paper›PMID 29767307›Full record

ArticleJournal of neuro-oncology2018

Virus vector-mediated genetic modification of brain tumor stromal cells after intravenous delivery.

Adrienn Volak, Stanley G LeRoy, Jeya Shree Natasan, David J Park, Pike See Cheah, Andreas Maus, Zachary Fitzpatrick, Eloise Hudry, Kelsey Pinkham, Sheetal Gandhi and 7 more

Open access · greenAbstract read
In one paragraph

Article in Journal of neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
2.4field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. Extracellular vesicles-associated AAVs for the treatment of Machado-Joseph disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  7. Review
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  9. Review
  10. Gene replacement therapy in a schwannoma mouse model of neurofibromatosis type 2.Molecular therapy. Methods & clinical development · 2022
    Article
  11. Review
  12. Review
  13. Article
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  15. Article
  16. Review
  17. Review
  18. Article
  19. Engineering of Exosomes to Target Cancer Metastasis.Cellular and molecular bioengineering · 2020
    Review
  20. Cloaked Viruses and Viral Factors in Cutting Edge Exosome-Based Therapies.Frontiers in cell and developmental biology · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 4 institutions in 2 countries.

Adrienn VolakDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Stanley G LeRoyDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Jeya Shree NatasanDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
David J ParkDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Pike See CheahDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Andreas MausDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Zachary FitzpatrickDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Eloise HudryDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Kelsey PinkhamDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Sheetal GandhiDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Bradley T HymanDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Dakai MuDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA.
Dwijit GuhaSarkarUniversity of Massachusetts Medical School, Worcester, MA, USA.
Anat O Stemmer-RachamimovMolecular Pathology Division, The Massachusetts General Hospital, Boston, MA, USA.
Miguel Sena-EstevesUniversity of Massachusetts Medical School, Worcester, MA, USA.
Christian E BadrDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA. badr.christian@mgh.harvard.edu.
Casey A MaguireDepartment of Neurology, The Massachusetts General Hospital, and NeuroDiscovery Center, Harvard Medical School, Boston, MA, USA. cmaguire@mgh.harvard.edu.ORCID http://orcid.org/0000-0001-8681-5179
Harvard University · USUniversity of Massachusetts Chan Medical School · USMassachusetts General Hospital · USUniversiti Putra Malaysia · MY

Funding

Identifying vulnerabilities and therapeutic targets in Glioma Stem CellsK22CA197053 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BADR, CHRISTIAN ELIAS · 2015 to 2017
$603k
National Cancer Institute K22CA197053NCI NIH HHS K22 CA197053
6 · The paper itself

Abstract

The malignant primary brain tumor, glioblastoma (GBM) is generally incurable. New approaches are desperately needed. Adeno-associated virus (AAV) vector-mediated delivery of anti-tumor transgenes is a promising strategy, however direct injection leads to focal transgene spread in tumor and rapid tumor division dilutes out the extra-chromosomal AAV genome, limiting duration of transgene expression. Intravenous (IV) injection gives widespread distribution of AAV in normal brain, however poor transgene expression in tumor, and high expression in non-target cells which may lead to ineffective therapy and high toxicity, respectively. Delivery of transgenes encoding secreted, anti-tumor proteins to tumor stromal cells may provide a more stable and localized reservoir of therapy as they are more differentiated than fast-dividing tumor cells. Reactive astrocytes and tumor-associated macrophage/microglia (TAMs) are stromal cells that comprise a large portion of the tumor mass and are associated with tumorigenesis. In mouse models of GBM, we used IV delivery of exosome-associated AAV vectors driving green fluorescent protein expression by specific promoters (NF-κB-responsive promoter and a truncated glial fibrillary acidic protein promoter), to obtain targeted transduction of TAMs and reactive astrocytes, respectively, while avoiding transgene expression in the periphery. We used our approach to express the potent, yet toxic anti-tumor cytokine, interferon beta, in tumor stroma of a mouse model of GBM, and achieved a modest, yet significant enhancement in survival compared to controls. Noninvasive genetic modification of tumor microenvironment represents a promising approach for therapy against cancers. Additionally, the vectors described here may facilitate basic research in the study of tumor stromal cells in situ.

Indexed as

Genetic TherapyAnimalsAstrocytesBrain NeoplasmsDependovirusDisease Models, AnimalFemaleGreen Fluorescent ProteinsInterferon-betaMiceMice, Inbred C57BLMice, NudePromoter Regions, GeneticStromal CellsGreen Fluorescent ProteinsInterferon-betaAAVAdeno-associated virus vectorsCancer gene therapyGlioblastomaGliomaReactive astrocytesTumor-associated myeloid-derived cellsTumor stroma

Identifiers

PMID29767307
PMCPMC6454875
OpenAlexW2804238454

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

Registered trials

None linked

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.