Evidence map›Paper›PMID 33479234›Full record

ArticleNature communications2021

Preclinical assessment of the efficacy and specificity of GD2-B7H3 SynNotch CAR-T in metastatic neuroblastoma.

Babak Moghimi, Sakunthala Muthugounder, Samy Jambon, Rachelle Tibbetts, Long Hung, Hamid Bassiri, Michael D Hogarty, David M Barrett, Hiroyuki Shimada, Shahab Asgharzadeh

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 2 pooled it
10.5field-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

103 citing papers in PubMed, 2 syntheses or guidelines pooled it, 149 citations in OpenAlex.

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  18. 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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43 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

10 authors at 3 institutions in 1 country.

Babak MoghimiChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.
Sakunthala MuthugounderChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.
Samy JambonChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.ORCID 0000-0001-7236-3239
Rachelle TibbettsChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.
Long HungChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.
Hamid BassiriChildren's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA.ORCID 0000-0001-6532-8478
Michael D HogartyChildren's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA.ORCID 0000-0002-9221-4852
David M BarrettChildren's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Hiroyuki ShimadaChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA.
Shahab AsgharzadehChildren's Hospital Los Angeles, Children's Center for Cancer and Blood Diseases, Division of Hematology, Oncology and Blood & Marrow Transplantation, and The Saban Research Institute, Los Angeles, CA, USA. sasgharzadeh@chla.usc.edu.
Children's Hospital of Los Angeles · USChildren's Hospital of Philadelphia · USUniversity of Southern California · US

Funding

Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI Kimberly Stegmaier · 2017 to 2026
$20.7M
CANCER RESEARCH TRAINING PROGRAMT32CA009615 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Gregory L Beatty, MICHAEL D HOGARTY · 1988 to 2026
$10.4M
Training Physician Scientists in Pediatric OncologyT32CA009659 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI DECLERCK, YVES A · 1991 to 2020
$2.2M
NCI NIH HHS P01 CA217959NCI NIH HHS T32 CA009615NCI NIH HHS T32 CA009659
6 · The paper itself

Abstract

The ability to utilize preclinical models to predict the clinical toxicity of chimeric antigen receptor (CAR) T cells in solid tumors is tenuous, thereby necessitating the development and evaluation of gated systems. Here we found that murine GD2 CAR-T cells, specific for the tumor-associated antigen GD2, induce fatal neurotoxicity in a costimulatory domain-dependent manner. Meanwhile, human B7H3 CAR-T cells exhibit efficacy in preclinical models of neuroblastoma. Seeking a better CAR, we generated a SynNotch gated CAR-T, GD2-B7H3, recognizing GD2 as the gate and B7H3 as the target. GD2-B7H3 CAR-T cells control the growth of neuroblastoma in vitro and in metastatic xenograft mouse models, with high specificity and efficacy. These improvements come partly from the better metabolic fitness of GD2-B7H3 CAR-T cells, as evidenced by their naïve T-like post-cytotoxicity oxidative metabolism and lower exhaustion profile.

Indexed as

AnimalsCell Line, TumorCell SurvivalCytotoxicity, ImmunologicGangliosidesHumansImmunotherapy, AdoptiveMiceMice, 129 StrainMice, Inbred C57BLNeoplasm MetastasisNeuroblastomaReceptors, Antigen, T-CellReceptors, Chimeric AntigenTumor BurdenXenograft Model Antitumor Assaysganglioside, GD2GangliosidesReceptors, Antigen, T-CellReceptors, Chimeric Antigen

Identifiers

PMID33479234
PMCPMC7820416
OpenAlexW3124707330

What OpenQuestion holds

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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.