Evidence map›Paper›PMID 31142380›Full record

ArticleJournal for immunotherapy of cancer2019

Improved efficacy against malignant brain tumors with EGFRwt/EGFRvIII targeting immunotoxin and checkpoint inhibitor combinations.

Vidyalakshmi Chandramohan, Xuhui Bao, Xin Yu, Scott Parker, Charlotte McDowall, Yen-Rei Yu, Patrick Healy, Annick Desjardins, Michael D Gunn, Matthias Gromeier and 3 more

Open access · goldAbstract read
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 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. EGFR: New Insights on Its Activation and Mutation in Tumor and Tumor Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. An overview of current therapeutic strategies for glioblastoma and the role of CD73 as an alternative curative approach.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022
    Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Preparation of a novel EGFR specific immunotoxin and its efficacy of anti-colorectal cancer in vitro and in vivo.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
    Article
  19. Review
  20. New Immunotherapeutic Approaches for Glioblastoma.Journal of immunology research · 2021
    Review
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 4 institutions in 2 countries.

Vidyalakshmi ChandramohanDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA. vidyalakshmi.chandramohan@duke.edu.ORCID 0000-0002-0653-3014
Xuhui BaoDepartment of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
Xin YuDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Scott ParkerDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Charlotte McDowallDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Yen-Rei YuDepartment of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Patrick HealyDuke Cancer Institute Biostatistics, Duke University Medical Center, Durham, NC, 27710, USA.
Annick DesjardinsDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Michael D GunnDepartment of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Matthias GromeierDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Smita K NairDepartment of Surgery, Duke University Medical Center, Durham, NC, 27710, USA.
Ira H PastanLaboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Darell D BignerDepartment of Neurosurgery and the Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Medical Sciences Research Building, Rm 181c, Box 3156, Durham, NC, 27710, USA.
Duke University · USDuke Medical Center · USCancer Institute (WIA) · INNational Institutes of Health · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Immunotoxin Therapy of Solid and Hematopoietic Tumors: Preclinical StudiesZIABC008753 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI PASTAN, IRA · 2009 to 2024
$33.1M
Vaccine Immunotoxin and Radioimmunotherapy of Primary and Metastatic CNS TumorsP01CA154291 · NCI · DUKE UNIVERSITY · PI BIGNER, DARELL D · 2012 to 2016
$14.5M
Oncolytic Polovirus, Immunotoxin, and Checkpoint Inhibitor Therapy of GliomasR35CA197264 · NCI · DUKE UNIVERSITY · PI BIGNER, DARELL D · 2015 to 2021
$6.1M
NCI NIH HHS P01 CA154291NCI NIH HHS P30 CA014236NCI NIH HHS R35 CA197264
6 · The paper itself

Abstract

backgroundD2C7-IT is a novel immunotoxin (IT) targeting wild-type epidermal growth factor receptor (EGFRwt) and mutant EGFR variant III (EGFRvIII) proteins in glioblastoma. In addition to inherent tumoricidal activity, immunotoxins induce secondary immune responses through the activation of T cells. However, glioblastoma-induced immune suppression is a major obstacle to an effective and durable immunotoxin-mediated antitumor response. We hypothesized that D2C7-IT-induced immune response could be effectively augmented in combination with αCTLA-4/αPD-1/αPD-L1 therapies in murine models of glioma.

methodsTo study this, we overexpressed the D2C7-IT antigen, murine EGFRvIII (dmEGFRvIII), in established glioma lines, CT-2A and SMA560. The reactivity and therapeutic efficacy of D2C7-IT against CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII cells was determined by flow cytometry and in vitro cytotoxicity assays, respectively. Antitumor efficacy of D2C7-IT was examined in immunocompetent, intracranial murine glioma models and the role of T cells was assessed by CD4+ and CD8+ T cell depletion. In vivo efficacy of D2C7-IT/αCTLA-4/αPD-1 monotherapy or D2C7-IT+αCTLA-4/αPD-1 combination therapy was evaluated in subcutaneous unilateral and bilateral CT-2A-dmEGFRvIII glioma-bearing immunocompetent mice. Further, antitumor efficacy of D2C7-IT+αCTLA-4/αPD-1/αPD-L1/αTim-3/αLag-3/αCD73 combination therapy was evaluated in intracranial CT-2A-dmEGFRvIII and SMA560-dmEGFRvIII glioma-bearing mice. Pairwise differences in survival curves were assessed using the generalized Wilcoxon test.

resultsD2C7-IT effectively killed CT-2A-dmEGFRvIII (IC

conclusionsThese data support the development of D2C7-IT and immune checkpoint blockade combinations for patients with malignant glioma.

Indexed as

AnimalsBrain NeoplasmsCell Line, TumorDisease Models, AnimalErbB ReceptorsFemaleHumansImmunotoxinsMiceMice, Inbred C57BLErbB ReceptorsImmunotoxinsEGFRImmune checkpoint inhibitorsImmunotoxinMalignant gliomasT cells

Identifiers

PMID31142380
PMCPMC6542114
OpenAlexW2947248704

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.