Evidence map›Paper›PMID 29975720›Full record

ArticlePloS one2018

Development of third generation anti-EGFRvIII chimeric T cells and EGFRvIII-expressing artificial antigen presenting cells for adoptive cell therapy for glioma.

Ayguen Sahin, Carlos Sanchez, Szofia Bullain, Peter Waterman, Ralph Weissleder, Bob S Carter

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.0field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 34 citations in OpenAlex.

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  15. Updated Insights on EGFR Signaling Pathways in Glioma.International journal of molecular sciences · 2021
    Review
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  17. New Immunotherapeutic Approaches for Glioblastoma.Journal of immunology research · 2021
    Review
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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

6 authors at 1 institution in 1 country.

Ayguen SahinHMS-MGH Center for Nervous System Repair, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States of America.ORCID 0000-0001-9247-8383
Carlos SanchezHMS-MGH Center for Nervous System Repair, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States of America.
Szofia BullainHMS-MGH Center for Nervous System Repair, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States of America.
Peter WatermanCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, United States of America.
Ralph WeisslederCenter for Systems Biology, Massachusetts General Hospital, Boston, MA, United States of America.
Bob S CarterHMS-MGH Center for Nervous System Repair, Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, United States of America.
Massachusetts General Hospital · US

Funding

The role of microvesicles in giloma virotherapyP01CA069246 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHAREST, ALAIN · 1996 to 2021
$30.9M
Training Program in Cancer Biology and TherapeuticsT32CA071345 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Daniel A. Haber, Lecia V. Sequist · 1997 to 2026
$10.6M
NCI NIH HHS P01 CA069246NCI NIH HHS T32 CA071345
6 · The paper itself

Abstract

Glioblastoma multiforme (GBM) is the most aggressive and deadly form of adult brain cancer. Despite of many attempts to identify potential therapies for this disease, including promising cancer immunotherapy approaches, it remains incurable. To address the need of improved persistence, expansion, and optimal antitumor activity of T-cells in the glioma milieu, we have developed an EGFRvIII-specific third generation (G3-EGFRvIII) chimeric antigen receptor (CAR) that expresses both co-stimulatory factors CD28 and OX40 (MR1-CD8TM-CD28-OX40-CD3ζ). To enhance ex vivo target specific activation and optimize T-cell culturing conditions, we generated artificial antigen presenting cell lines (aAPC) expressing the extracellular and transmembrane domain of EGFRvIII (EGFRVIIIΔ654) with costimulatory molecules including CD32, CD80 and 4-1BBL (EGFRVIIIΔ654 aAPC and CD32-80-137L-EGFRVIIIΔ654 aAPC). We demonstrate that the highest cell growth was achieved when G3-EGFRvIII CAR T-cells were cocultured with both co-stimulatory aAPCs and with exposure to EGFRvIII (CD32-80-137L-EGFRVIIIΔ654 aAPCs) in culturing periods of three to six weeks. G3-EGFRvIII CAR T-cells showed an increased level of IFN-γ when cocultured with CD32-80-137L-EGFRVIIIΔ654 aAPCs. Evaluation of G3-EGFRvIII CAR T-cells in an orthotropic human glioma xenograft model demonstrated a prolonged survival of G3-EGFRvIII CAR treated mice compared to control mice. Importantly, we observed survival of G3-EGFRvIII CAR T-cells within the tumor as long as 90 days after implantation in low-dose and single administration, accompanied by a marked tumor stroma demolition. These findings suggest that G3-EGFRvIII CAR cocultured with CD32-80-137L-EGFRVIIIΔ654 aAPCs warrants itself as a potential anti-tumor therapy strategy for glioblastoma.

Indexed as

Gene ExpressionImmunotherapy, AdoptiveAnimalsAntigen-Presenting CellsCell Line, TumorCytokinesCytotoxicity, ImmunologicDisease Models, AnimalErbB ReceptorsFemaleGene OrderGenetic VectorsGliomaHumansMiceReceptors, Chimeric AntigenCytokinesepidermal growth factor receptor VIIIErbB ReceptorsReceptors, Chimeric Antigen

Identifiers

PMID29975720
PMCPMC6033533
OpenAlexW2837347123

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.