Evidence map›Paper›PMID 29769444›Full record

ArticleJCI insight2018

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity.

Dongrui Wang, Brenda Aguilar, Renate Starr, Darya Alizadeh, Alfonso Brito, Aniee Sarkissian, Julie R Ostberg, Stephen J Forman, Christine E Brown

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 154 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
154citing papers in PubMed, 1 pooled it
9.0field-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

154 citing papers in PubMed, 1 synthesis or guideline pooled it, 228 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Generation of effector CD4Stem cell reports · 2026
    Article
  8. Depletion of CD8Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Reversing T cell dysfunction in a novelFrontiers in immunology · 2026
    Article
  18. Article
  19. EomesoderminImmunity · 2025
    Article
  20. Article

94 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

9 authors at 2 institutions in 2 countries.

Dongrui WangDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Brenda AguilarDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Renate StarrDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Darya AlizadehDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Alfonso BritoDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Aniee SarkissianDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Julie R OstbergDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Stephen J FormanDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
Christine E BrownDepartment of Hematology and Hematopoietic Cell Transplantation, T Cell Therapeutics Research Laboratory, and.
CTI BioPharma (United Kingdom) · GBCity Of Hope National Medical Center · US

Funding

Transgenic Mouse FacilityP30CA033572 · NCI · CITY OF HOPE/BECKMAN RESEARCH INSTITUTE · PI STANLEY R. HAMILTON · 1985 to 2026
$86.3M
FDA HHS R01 FD005129NCI NIH HHS P30 CA033572
6 · The paper itself

Abstract

Chimeric antigen receptor-modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.

Indexed as

CD8-Positive T-LymphocytesGlioblastomaHumansBrain cancerImmunologyOncologyT cells

Identifiers

PMID29769444
PMCPMC6012522
OpenAlexW2803369586

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.