Evidence map›Paper›PMID 36631162›Full record

ArticleJournal for immunotherapy of cancer2023

Preclinical optimization of a GPC2-targeting CAR T-cell therapy for neuroblastoma.

Ming Sun, Yingying Cao, Reona Okada, Jeyshka M Reyes-González, Hannah G Stack, Haiying Qin, Nan Li, Charlie Seibert, Michael C Kelly, Eytan Ruppin and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
6.7field-weighted citation impact, top 3% 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

31 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Development of novel GPC2-directed radiotheranostics and CAR T cell therapy for neuroblastoma.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
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  6. Review
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  12. D3-GPC2-Directed CAR T Cells Are Safe and Efficacious in Preclinical Models of Neuroblastoma and Small Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025
    Article
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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

13 authors at 4 institutions in 1 country.

Ming SunPediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Yingying CaoCancer Data Science Laboratory, NCI, Bethesda, Maryland, USA.
Reona OkadaPediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Jeyshka M Reyes-GonzálezPediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Hannah G StackPediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Haiying QinPediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Nan LiLaboratory of Molecular Biology, National Institutes of Health, Bethesda, Maryland, USA.
Charlie SeibertCenter for Cancer Research Single Cell Analysis Facility, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
Michael C KellySingle Cell Analysis Facility, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Eytan RuppinCancer Data Science Laboratory, NCI, Bethesda, Maryland, USA.ORCID 0000-0003-4299-7657
Mitchell HoLaboratory of Molecular Biology, National Institutes of Health, Bethesda, Maryland, USA.
Carol J ThielePediatric Oncology Branch, NCI, Bethesda, Maryland, USA.
Rosa NguyenPediatric Oncology Branch, NCI, Bethesda, Maryland, USA hongharosa.nguyen@nih.gov.ORCID 0000-0001-5143-2055
Center for Cancer Research · USNational Institutes of Health · USFrederick National Laboratory for Cancer Research · USNational Cancer Institute · US

Funding

WORK ORDER 126643 B539 EXPAND IC SUITE75N91019D00024 · NIAID · LEIDOS BIOMEDICAL RESEARCH, INC. · PI BRISCOE, LYNN · 2019 to 2025
$3932.6M
Regulation of Differentiation of Pediatric Embryonal Tumors- NeuroblastomaZIABC010788 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI THIELE, CAROL J · 2009 to 2025
$29.7M
Development of new antibody-based cancer therapiesZIABC010891 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HO, MITCHELL · 2009 to 2025
$21.4M
Neuroblastoma Tumor Microenvironment: tumor growth and immune regulationZIABC012046 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI THIELE, CAROL J · 2021 to 2025
$9.0M
Single Cell Analysis FacilityZICBC012123 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI KELLY, MICHAEL · 2022 to 2025
$7.3M
Development of new therapies for neuroblastomaZIABC012066 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NGUYEN, HONG HA ROSA · 2022 to 2025
$5.6M
Redox imaging for breast cancer prognosisR01CA191207 · NCI · UNIVERSITY OF PENNSYLVANIA · PI LI, LIN Z · 2015 to 2019
$3.2M
Regulation of Differentiation of Pediatric Embryonal Tumors- NeuroblastomaZ01BC010788 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI THIELE, CAROL J · 2007 to 2008
$1.2M
Intramural NIH HHS Z01 BC010788Intramural NIH HHS ZIA BC010788Intramural NIH HHS ZIA BC012066NCI NIH HHS 75N91019D00024NCI NIH HHS R01 CA191207
6 · The paper itself

Abstract

backgroundAlthough most patients with newly diagnosed high-risk neuroblastoma (NB) achieve remission after initial therapy, more than 50% experience late relapses caused by minimal residual disease (MRD) and succumb to their cancer. Therapeutic strategies to target MRD may benefit these children. We developed a new chimeric antigen receptor (CAR) targeting glypican-2 (GPC2) and conducted iterative preclinical engineering of the CAR structure to maximize its anti-tumor efficacy before clinical translation.

methodsWe evaluated different GPC2-CAR constructs by measuring the CAR activity in vitro. NOD-SCID mice engrafted orthotopically with human NB cell lines or patient-derived xenografts and treated with human CAR T cells served as in vivo models. Mechanistic studies were performed using single-cell RNA-sequencing.

resultsApplying stringent in vitro assays and orthotopic in vivo NB models, we demonstrated that our single-chain variable fragment, CT3, integrated into a CAR vector with a CD28 hinge, CD28 transmembrane, and 4-1BB co-stimulatory domain (CT3.28H.BBζ) elicits the best preclinical anti-NB activity compared with other tested CAR constructs. This enhanced activity was associated with an enrichment of CD8

conclusionGiven the robust preclinical activity of CT3.28H.BBζ, these results form a promising basis for further clinical testing in children with NB.

Indexed as

GlypicansNeuroblastomaReceptors, Chimeric AntigenAnimalsCD28 AntigensChildGangliosidesHumansImmunotherapy, AdoptiveMiceMice, Inbred NODMice, SCIDCD28 AntigensGangliosidesGlypicansReceptors, Chimeric Antigenimmunotherapyneuroblastomapediatricsreceptors, chimeric antigen

Identifiers

PMID36631162
PMCPMC9835961
OpenAlexW4315644794

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.