Evidence map›Paper›PMID 22780919›Full record

ArticleHuman gene therapy2012

Recognition of glioma stem cells by genetically modified T cells targeting EGFRvIII and development of adoptive cell therapy for glioma.

Richard A Morgan, Laura A Johnson, Jeremy L Davis, Zhili Zheng, Kevin D Woolard, Elizabeth A Reap, Steven A Feldman, Nachimuthu Chinnasamy, Chien-Tsun Kuan, Hua Song and 3 more

Abstract read
In one paragraph

Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 198 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
198citing papers in PubMed, 3 pooled it
12.5field-weighted citation impact, top 1% 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

198 citing papers in PubMed, 3 syntheses or guidelines pooled it, 311 citations in OpenAlex.

  1. Pooled it
  2. The growing world of CAR T cell trials: a systematic review.Cancer immunology, immunotherapy : CII · 2016
    Pooled it
  3. Guideline
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  8. Article
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  11. Article
  12. From Bench to Bedside: Emerging Paradigms in CAR-T Cell Therapy for Solid Malignancies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
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  16. Article
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138 more citing papers are in PubMed but not listed here.

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

13 authors at 2 institutions in 1 country.

Richard A MorganSurgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. rmorgan@mail.nih.gov
Laura A Johnson
Jeremy L Davis
Zhili Zheng
Kevin D Woolard
Elizabeth A Reap
Steven A Feldman
Nachimuthu Chinnasamy
Chien-Tsun Kuan
Hua Song
Wei Zhang
Howard A Fine
Steven A Rosenberg
National Institutes of Health · USDuke Medical Center · US

Funding

Adoptive Cell Transfer Immunotherapy of CancerZIABC010984 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROSENBERG, STEVEN · 2009 to 2025
$56.8M
Clinical production of viral vectors for cancer gene therapyZICBC010989 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI BEYER, RACHEL · 2009 to 2025
$12.6M
Intramural NIH HHS
6 · The paper itself

Abstract

No curative treatment exists for glioblastoma, with median survival times of less than 2 years from diagnosis. As an approach to develop immune-based therapies for glioblastoma, we sought to target antigens expressed in glioma stem cells (GSCs). GSCs have multiple properties that make them significantly more representative of glioma tumors than established glioma cell lines. Epidermal growth factor receptor variant III (EGFRvIII) is the result of a novel tumor-specific gene rearrangement that produces a unique protein expressed in approximately 30% of gliomas, and is an ideal target for immunotherapy. Using PCR primers spanning the EGFRvIII-specific deletion, we found that this tumor-specific gene is expressed in three of three GCS lines. Based on the sequence information of seven EGFRvIII-specific monoclonal antibodies (mAbs), we assembled chimeric antigen receptors (CARs) and evaluated the ability of CAR-engineered T cells to recognize EGFRvIII. Three of these anti-EGFRvIII CAR-engineered T cells produced the effector cytokine, interferon-γ, and lysed antigen-expressing target cells. We concentrated development on a CAR produced from human mAb 139, which specifically recognized GSC lines and glioma cell lines expressing mutant EGFRvIII, but not wild-type EGFR and did not recognize any normal human cell tested. Using the 139-based CAR, T cells from glioblastoma patients could be genetically engineered to recognize EGFRvIII-expressing tumors and could be expanded ex vivo to large numbers, and maintained their antitumor activity. Based on these observations, a γ-retroviral vector expressing this EGFRvIII CAR was produced for clinical application.

Indexed as

Immunotherapy, AdoptiveAnimalsAntibodies, MonoclonalBrain NeoplasmsCell- and Tissue-Based TherapyCell Line, TumorErbB ReceptorsGenetic EngineeringGenetic VectorsGliomaHumansMiceNeoplastic Stem CellsNIH 3T3 CellsReceptors, AntigenT-LymphocytesAntibodies, Monoclonalepidermal growth factor receptor VIIIErbB ReceptorsReceptors, Antigen

Identifiers

PMID22780919
PMCPMC3472555
OpenAlexW2009914447

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.