Evidence map›Paper›PMID 40411488›Full record

ArticleNeuro-oncology2025

Transient mRNA CAR T cells targeting GD2 provide dose-adjusted efficacy against diffuse midline glioma and high-grade glioma models.

Jessica B Foster, Peter J Madsen, Kyra Harvey, Crystal Griffin, Allison Stern, Luke Patterson, Nikhil Joshi, Conor Dickson, Olivia McManus, Ezra Beaubien and 9 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

15 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  11. Current Status and Evolution of Immunotherapy in Glioma Management.International journal of medical sciences · 2026
    Review
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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

19 authors.

Jessica B FosterDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Peter J MadsenCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Kyra HarveyDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Crystal GriffinDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Allison SternDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Luke PattersonDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nikhil JoshiDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Conor DicksonCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Olivia McManusDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ezra BeaubienDivision of Oncology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Cullen WilsonCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
David R BealeCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Valerie BaubetCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Peeyush N GoelCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nicholas A VitanzaDepartment of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA, USA.
Javad NazarianDepartment of Pediatrics, University Children's Hospital, University of Zurich, Zurich, Switzerland.ORCID 0000-0002-1951-9828
Mateusz KoptyraCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Phillip B StormCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Adam C ResnickCenter for Data Driven Discovery in Biomedicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Funding

Defining a therapeutic platform for DIPG with mRNA CAR T cells and microglia inhibitionK08CA263179 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI FOSTER, JESSICA B · 2021 to 2025
$905k
Department of Defense W81XWH-21-1-0221Greyson Saves FoundationKourtney Rose FoundationLiv Like a UnicornMatthew Larson FoundationNational Institute of Health 5 K08 CA263179NCI NIH HHS K08 CA263179October Saves
6 · The paper itself

Abstract

backgroundDiffuse midline glioma (DMG) and high-grade glioma are devastating pediatric central nervous system tumors that remain incurable. Recent chimeric antigen receptor (CAR) T cell studies have shown proof of concept and early signs of efficacy against DMG targeting GD2. Prior work and ongoing clinical trials have focused on using viral vectors to create permanent CAR T cells. However, virally transduced GD2-directed CAR T cells have shown significant neurotoxicity in both preclinical models and human trials.

methodsWe evaluated transient CAR T cells targeting GD2 created with mRNA, assessing for efficacy and safety in cell line, organoid, and in vivo xenograft models with repetitive intratumoral dosing.

resultsWe show that mRNA GD2-directed CAR T cells are active against both cell lines and organoid models of DMG and high-grade glioma in vitro. Cytotoxicity consistently abates over 9 days, highlighting the potential to avoid toxicity from persistent T cell activity. In both pontine and thalamic DMG xenograft models, repeated doses of mRNA GD2-directed CAR T cells were titrated down to maintain therapeutic effects without causing neurologic toxicity.

conclusionsOur results demonstrate the utility of transient mRNA CAR T cells delivered intratumorally to provide effective tumor killing with a defined half-life, allowing for modulation of the dose and potential side effects. We anticipate this study will expand the use of CAR T cell therapy for DMG and other central nervous system tumors and non-malignant disorders, where concern for toxicity from permanently expressing CAR T cells may hinder development.

Indexed as

Brain NeoplasmsGangliosidesGliomaImmunotherapy, AdoptiveReceptors, Chimeric AntigenRNA, MessengerT-LymphocytesAnimalsFemaleHumansMiceTumor Cells, CulturedXenograft Model Antitumor Assaysganglioside, GD2GangliosidesReceptors, Chimeric AntigenRNA, Messengerbrain tumorCAR T cellsdiffuse midline gliomamRNApediatric

Identifiers

PMID40411488
PMCPMC12833531

What OpenQuestion holds

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LicenceCC BY
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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.