Evidence map›Paper›PMID 27756784›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2017

TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells.

Hung C Tran, Zesheng Wan, Michael A Sheard, Jianping Sun, Jeremy R Jackson, Jemily Malvar, Yibing Xu, Larry Wang, Richard Sposto, Eugene S Kim and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed
7.0field-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

95 citing papers in PubMed, 129 citations in OpenAlex.

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  12. Reprogramming natural killer cells for cancer therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Hung C TranChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Zesheng WanChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Michael A SheardChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Jianping SunChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Jeremy R JacksonChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Jemily MalvarChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Yibing XuChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Larry WangDepartment of Pathology and Laboratory Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Richard SpostoChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Eugene S KimChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Shahab AsgharzadehChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California.
Robert C SeegerChildren's Hospital Los Angeles and the Saban Research Institute, Los Angeles, California. rseeger@chla.usc.edu.
University of Southern California · USChildren's Hospital of Los Angeles · US

Funding

Vascular endothelial cell integrins in angiogenesisP01CA081403 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI SEEGER, ROBERT CHARLES · 2000 to 2014
$28.5M
Tumor microenvironment-dependent therapy resistanceP01CA217959 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$20.7M
Molecular Diagnostics for Risk Stratification and Monitoring of NeuroblastomaR01CA182633 · NCI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI ASGHARZADEH, SHAHAB, SEEGER, ROBERT CHARLES · 2014 to 2016
$2.0M
NCI NIH HHS P01 CA081403NCI NIH HHS P01 CA217959NCI NIH HHS R01 CA182633
6 · The paper itself

Abstract

purposeImmunotherapy of high-risk neuroblastoma using the anti-GD2 antibody dinutuximab induces antibody-dependent cell-mediated cytotoxicity (ADCC). Galunisertib, an inhibitor of TGFβR1, was examined for its ability to enhance the efficacy of dinutuximab in combination with human ex vivo activated NK (aNK) cells against neuroblastoma. EXPERIMENTAL

designTGFB1 and TGFBR1 mRNA expression was determined for 249 primary neuroblastoma tumors by microarray analysis. The ability of galunisertib to inhibit SMAD activity induced by neuroblastoma patient blood and bone marrow plasmas in neuroblastoma cells was tested. The impact of galunisertib on TGFβ1-induced inhibition of aNK cytotoxicity and ADCC in vitro and on anti-neuroblastoma activity in NOD-scid gamma (NSG) mice was determined.

resultsNeuroblastomas express TGFB1 and TGFBR1 mRNA. Galunisertib suppressed SMAD activation in neuroblastoma cells induced by exogenous TGFβ1 or by patient blood and bone marrow plasma, and suppressed SMAD2 phosphorylation in human neuroblastoma cells growing in NSG mice. In NK cells treated in vitro with exogenous TGFβ1, galunisertib suppressed SMAD2 phosphorylation and restored the expression of DNAM-1, NKp30, and NKG2D cytotoxicity receptors and the TRAIL death ligand, the release of perforin and granzyme A, and the direct cytotoxicity and ADCC of aNK cells against neuroblastoma cells. Addition of galunisertib to adoptive cell therapy with aNK cells plus dinutuximab reduced tumor growth and increased survival of mice injected with two neuroblastoma cell lines or a patient-derived xenograft.

conclusionsGalunisertib suppresses activation of SMAD2 in neuroblastomas and aNK cells, restores NK cytotoxic mechanisms, and increases the efficacy of dinutuximab with aNK cells against neuroblastoma tumors. Clin Cancer Res; 23(3); 804-13. ©2016 AACRSee related commentary by Zenarruzabeitia et al., p. 615.

Indexed as

AnimalsAntibodies, MonoclonalAntineoplastic Agents, ImmunologicalCell Line, TumorCytotoxicity, ImmunologicDrug SynergismFemaleGene Expression ProfilingHumansImmunotherapy, AdoptiveKiller Cells, NaturalMaleMiceMice, Inbred NODNeoplasm ProteinsNeuroblastomaAntibodies, MonoclonalAntineoplastic Agents, ImmunologicaldinutuximabLY-2157299Neoplasm ProteinsProtein Serine-Threonine KinasesPyrazolesQuinolinesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IRNA, MessengerRNA, NeoplasmSmad2 ProteinSMAD2 protein, humanTGFB1 protein, humanTGFBR1 protein, humanTgfbr1 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID27756784
PMCPMC5361893
OpenAlexW2531805832

What OpenQuestion holds

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Read underepoch 390

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.