Evidence map›Paper›PMID 31466914›Full record

ArticleEBioMedicine2019

B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres.

Dean Nehama, Natalia Di Ianni, Silvia Musio, Hongwei Du, Monica Patané, Bianca Pollo, Gaetano Finocchiaro, James J H Park, Denise E Dunn, Drake S Edwards and 7 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.

0numbers the graph read from it
0cells of the map it votes in
138citing papers in PubMed
8.6field-weighted citation impact, top 2% 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

138 citing papers in PubMed, 183 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. CAR-T Cell Therapy for Central Nervous System Tumors.Methods in molecular biology (Clifton, N.J.) · 2026
    Review
  10. Review
  11. Current Status and Evolution of Immunotherapy in Glioma Management.International journal of medical sciences · 2026
    Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

78 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 4 institutions in 2 countries.

Dean NehamaLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Natalia Di IanniLaboratory of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Silvia MusioLaboratory of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Hongwei DuLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Monica PatanéUnit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Bianca PolloUnit of Neuropathology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Gaetano FinocchiaroUnit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
James J H ParkDepartment of Radiation Oncology, Duke University Health System, Durham, NC, USA.
Denise E DunnDepartment of Radiation Oncology, Duke University Health System, Durham, NC, USA.
Drake S EdwardsDepartment of Radiation Oncology, Duke University Health System, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University Health System, Durham, NC, USA.
Jeffrey S DamrauerLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Hannah HudsonLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Scott R FloydDepartment of Radiation Oncology, Duke University Health System, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University Health System, Durham, NC, USA.
Soldano FerroneDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Barbara SavoldoLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Department of Pediatrics, University of North Carolina, Chapel Hill, NC, USA.
Serena PellegattaLaboratory of Immunotherapy of Brain Tumors, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy; Unit of Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy. Electronic address: serena.pellegatta@istituto-besta.it.
Gianpietro DottiLineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA; Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC, USA. Electronic address: gdotti@med.unc.edu.
Fondazione IRCCS Istituto Neurologico Carlo Besta · ITUniversity of North Carolina at Chapel Hill · USDuke University Health System · USHarvard University · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Targeted Alpha-Particle Radiotheraphy of Brain Tumors with 211At-81C6 AntibodyP50CA190991 · NCI · DUKE UNIVERSITY · PI SAMPSON, JOHN H. · 2014 to 2023
$20.8M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM008719 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI DARVILLE, TONI, DESHMUKH, MOHANISH P · 1999 to 2023
$15.1M
A 3D ex vivo orthotopic xenograft screening platform to identify radiosensitization targets and druggability in gliomaR21CA226483 · NCI · DUKE UNIVERSITY · PI FLOYD, SCOTT R · 2019 to 2020
$385k
IL-15 TRiKES-based specific immunotherapy of pancreatic ductal adenocarcinomaR03CA231766 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FERRONE, CRISTINA R., FERRONE, SOLDANO · 2018 to 2019
$177k
Safety and anti-tumor activity of B7-H3 CAR T cells in TNBCR03CA223886 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DOTTI, GIANPIETRO, FERRONE, SOLDANO · 2018 to 2019
$176k
NCI NIH HHS P50 CA190991NCI NIH HHS R03 CA223886NCI NIH HHS R03 CA231766NCI NIH HHS R21 CA226483NIGMS NIH HHS T32 GM007171NIGMS NIH HHS T32 GM008719
6 · The paper itself

Abstract

backgroundThe dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM.

methodsWe compared mRNA expression of antigens in GBM using TCGA data, and validated B7-H3 expression by immunohistochemistry. We then tested the antitumor activity of B7-H3-redirected CAR-T cells against GBM cell lines and patient-derived GBM neurospheres in vitro and in xenograft murine models.

findingsB7-H3 mRNA and protein are overexpressed in GBM relative to normal brain in all GBM subtypes. Of the 46 specimens analyzed by immunohistochemistry, 76% showed high B7-H3 expression, 22% had detectable, but low B7-H3 expression and 2% were negative, as was normal brain. All 20 patient-derived neurospheres showed ubiquitous B7-H3 expression. B7-H3-redirected CAR-T cells effectively targeted GBM cell lines and neurospheres in vitro and in vivo. No significant differences were found between CD28 and 4-1BB co-stimulation, although CD28-co-stimulated CAR-T cells released more inflammatory cytokines.

interpretationWe demonstrated that B7-H3 is highly expressed in GBM specimens and neurospheres that contain putative cancer stem cells, and that B7-H3-redirected CAR-T cells can effectively control tumor growth. Therefore, B7-H3 represents a promising target in GBM. FUND: Alex's Lemonade Stand Foundation; Il Fondo di Gio Onlus; National Cancer Institute; Burroughs Wellcome Fund.

Indexed as

AnimalsAntigens, NeoplasmB7 AntigensBiomarkersBrain NeoplasmsCell Line, TumorDisease Models, AnimalGlioblastomaHumansImmunophenotypingImmunotherapy, AdoptiveMiceNeoplastic Stem CellsReceptors, Antigen, T-CellReceptors, Chimeric AntigenT-LymphocytesAntigens, NeoplasmB7 AntigensBiomarkersCD276 protein, humanReceptors, Antigen, T-CellReceptors, Chimeric AntigenB7-H3Cancer stem cellsChimeric antigen receptorGlioblastomaImmunotherapy

Identifiers

PMID31466914
PMCPMC6796553
OpenAlexW2970981785

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.