Evidence map›Paper›PMID 27194146›Full record

ArticleNeuro-oncology2016

Systemic AAV9-IFNβ gene delivery treats highly invasive glioblastoma.

Dwijit GuhaSarkar, Qin Su, Guangping Gao, Miguel Sena-Esteves

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

30 citing papers in PubMed, 32 citations in OpenAlex.

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  13. Progress of nanoparticle drug delivery system for the treatment of glioma.Frontiers in bioengineering and biotechnology · 2024
    Review
  14. Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024
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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

4 authors at 1 institution in 1 country.

Dwijit GuhaSarkarHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., Q.S., G.G., M.S.-E.); Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., M.S.-E.); Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts (G.G.).
Qin SuHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., Q.S., G.G., M.S.-E.); Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., M.S.-E.); Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts (G.G.).
Guangping GaoHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., Q.S., G.G., M.S.-E.); Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., M.S.-E.); Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts (G.G.).
Miguel Sena-EstevesHorae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., Q.S., G.G., M.S.-E.); Department of Neurology, University of Massachusetts Medical School, Worcester, Massachusetts (D.G., M.S.-E.); Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts (G.G.).
University of Massachusetts Chan Medical School · US

Funding

Development of CNS-targeted AAV vectorsR01NS066310 · NINDS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ESTEVES, MIGUEL S · 2009 to 2012
$1.3M
NINDS NIH HHS R01 NS066310
6 · The paper itself

Abstract

backgroundComplete surgical removal of all glioblastoma (GBM) cells is impossible due to extensive infiltration into brain parenchyma that ultimately leads to tumor recurrence. The current standard of care affords modest improvements in survival. New therapeutic interventions are needed to prevent recurrence. Local AAV-hIFNβ gene delivery to the brain was previously shown to eradicate noninvasive orthotopic U87 tumors in mice. However, widespread CNS gene delivery may be necessary to treat invasive GBMs. Here we investigated the therapeutic effectiveness of systemically infused AAV9-hIFNβ against an invasive orthotopic GBM8 model.

methodsMice bearing human GBM8 brain tumors expressing firefly luciferase (Fluc) were treated systemically with different doses of scAAV9-hIFNβ vector. Therapeutic efficacy was assessed by sequential bioluminescence imaging of tumor Fluc activity and animal survival. Brains were analyzed post mortem for the presence and appearance of tumors. Two transcriptionally restricted AAV vectors were used to assess the therapeutic contribution of peripheral hIFNβ.

resultsSystemic infusion of scAAV9-hIFNβ vector induced complete regression of established GBM8 tumors in a dose-dependent manner. The efficacy of this approach was also dependent on the stage of tumor growth at the time of treatment. We also showed that peripherally produced hIFNβ contributed considerably to the therapeutic effect of scAAV9-hIFNβ. A comparative study of systemic and unilateral intracranial delivery of scAAV9-hIFNβ in a bilateral GBM8 tumor model showed the systemic route to be the most effective approach for treating widely dispersed tumors.

conclusionsSystemic delivery of AAV9-IFNβ is an attractive approach for invasive and multifocal GBM treatment.

Indexed as

Gene Transfer TechniquesAnimalsBrainBrain NeoplasmsCell Line, TumorDependovirusDose-Response Relationship, DrugGenetic TherapyGenetic VectorsGlioblastomaHumansInterferon-betaMiceMice, NudeInterferon-betaadeno associated virus (AAV)glioblastoma (GBM)interferon-beta (IFNβ)mouse orthotopic xenograftsystemic AAV gene therapy

Identifiers

PMID27194146
PMCPMC5063516
OpenAlexW2395758921

What OpenQuestion holds

Textmetadata
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.