Evidence map›Paper›PMID 31727131›Full record

ArticleJournal for immunotherapy of cancer2019

CRISPR-Cas9 disruption of PD-1 enhances activity of universal EGFRvIII CAR T cells in a preclinical model of human glioblastoma.

Bryan D Choi, Xiaoling Yu, Ana P Castano, Henia Darr, Daniel B Henderson, Amanda A Bouffard, Rebecca C Larson, Irene Scarfò, Stefanie R Bailey, Genevieve M Gerhard and 7 more

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

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 204 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
204citing papers in PubMed, 3 pooled it
13.6field-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

204 citing papers in PubMed, 3 syntheses or guidelines pooled it, 273 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
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  6. Review
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  14. Article
  15. Targeting PD-1Science advances · 2026
    Article
  16. Review
  17. Review
  18. Review
  19. Review
  20. The Role of CRISPR and Its Therapeutic Applications in Glioblastoma.International journal of molecular sciences · 2026
    Review

144 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

17 authors at 1 institution in 1 country.

Bryan D ChoiCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Xiaoling YuCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Ana P CastanoCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Henia DarrCRISPR Therapeutics, Cambridge, Massachusetts, USA.
Daniel B HendersonCRISPR Therapeutics, Cambridge, Massachusetts, USA.
Amanda A BouffardCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Rebecca C LarsonCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Irene ScarfòCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Stefanie R BaileyCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Genevieve M GerhardCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Matthew J FrigaultCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Mark B LeickCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Andrea SchmidtsCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA.
Jason G SagertCRISPR Therapeutics, Cambridge, Massachusetts, USA.
William T CurryDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Bob S CarterDepartment of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Marcela V MausCellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 3.216, Charlestown, Boston, Massachusetts, 02129, USA. mvmaus@mgh.harvard.edu.ORCID 0000-0002-7578-0393
Harvard University · US

Funding

Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
Neuroscience Resident Research ProgramR25NS065743 · NINDS · MASSACHUSETTS GENERAL HOSPITAL · PI CASH, SYDNEY S, WILLIAMS, ZIV · 2009 to 2023
$11.8M
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 K12 CA087723NCI NIH HHS T32 CA071345NINDS NIH HHS R25 NS065743
6 · The paper itself

Abstract

Despite remarkable success in the treatment of hematological malignancies, CAR T-cell therapies for solid tumors have floundered, in large part due to local immune suppression and the effects of prolonged stimulation leading to T-cell dysfunction and exhaustion. One mechanism by which gliomas and other cancers can hamper CAR T cells is through surface expression of inhibitory ligands such as programmed cell death ligand 1 (PD-L1). Using the CRIPSR-Cas9 system, we created universal CAR T cells resistant to PD-1 inhibition through multiplexed gene disruption of endogenous T-cell receptor (TRAC), beta-2 microglobulin (B2M) and PD-1 (PDCD1). Triple gene-edited CAR T cells demonstrated enhanced activity in preclinical glioma models. Prolonged survival in mice bearing intracranial tumors was achieved after intracerebral, but not intravenous administration. CRISPR-Cas9 gene-editing not only provides a potential source of allogeneic, universal donor cells, but also enables simultaneous disruption of checkpoint signaling that otherwise impedes maximal antitumor functionality.

Indexed as

ErbB ReceptorsImmunotherapy, AdoptiveAnimalsBrain NeoplasmsCell Line, TumorCRISPR-Cas SystemsGlioblastomaHumansMiceProgrammed Cell Death 1 ReceptorT-LymphocytesXenograft Model Antitumor Assaysepidermal growth factor receptor VIIIErbB ReceptorsPDCD1 protein, humanProgrammed Cell Death 1 ReceptorCRISPR-Cas systemsEGFRvIIIGlioblastomaReceptors, chimeric antigen

Identifiers

PMID31727131
PMCPMC6857271
OpenAlexW2985370419

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.