Evidence map›Paper›PMID 34244307›Full record

ArticleJournal for immunotherapy of cancer2021

Combinatorial immunotherapy of N-803 (IL-15 superagonist) and dinutuximab with ex vivo expanded natural killer cells significantly enhances in vitro cytotoxicity against GD2

Yaya Chu, Gaurav Nayyar, Susiyan Jiang, Jeremy M Rosenblum, Patrick Soon-Shiong, Jeffrey T Safrit, Dean A Lee, Mitchell S Cairo

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

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

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  11. Killing the killers: Natural killer cell therapy targeting glioma stem cells in high-grade glioma.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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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

8 authors at 3 institutions in 1 country.

Yaya ChuDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA mitchell_cairo@nymc.edu yaya_chu@nymc.edu.
Gaurav NayyarDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Susiyan JiangDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Jeremy M RosenblumDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA.
Patrick Soon-ShiongImmunityBio, Inc, Culver City, California, USA.
Jeffrey T SafritNantKwest, Culver City, California, USA.
Dean A LeeDepartment of Hem/Onc/BMT, Nationwide Children's Hospital, Columbus, Ohio, USA.
Mitchell S CairoDepartment of Pediatrics, New York Medical College, Valhalla, New York, USA mitchell_cairo@nymc.edu yaya_chu@nymc.edu.ORCID 0000-0002-2075-434X
New York Medical College · USImmunityBio (United States) · USNationwide Children's Hospital · US

Funding

Project 4:Targeting M2-like Macrophages and MDSC with Myelolytic-VirotherapyU54CA232561 · NCI · RESEARCH INST NATIONWIDE CHILDREN'S HOSP · PI CAIRO, MITCHELL S., CRIPE, TIMOTHY P · 2019 to 2023
$12.1M
Intravascular Integrin - Mediated Steps in Breast Cancer MetastasisR01CA160461 · NCI · UNIVERSITY OF MISSOURI-COLUMBIA · PI GLINSKII, VLADISLAV V · 2013 to 2017
$1.4M
NCI NIH HHS R01 CA160461NCI NIH HHS U54 CA232561
6 · The paper itself

Abstract

backgroundChildren with recurrent and/or metastatic osteosarcoma (OS), neuroblastoma (NB) and glioblastoma multiforme (GBM) have a dismal event-free survival (<25%). The majority of these solid tumors highly express GD2. Dinutuximab, an anti-GD2 monoclonal antibody, significantly improved event-free survival in children with GD2

methodsThe anti-tumor combinatorial effects of N-803, dinutuximab and ex vivo expanded peripheral blood NK cells (exPBNK) were performed in vitro using cytoxicity assays against GD2

resultsN-803 increased the viability and proliferation of exPBNK. The increased viability and proliferation are associated with increased phosphorylation of Stat3, Stat5, AKT, p38MAPK and the expression of NK activating receptors. The combination of dinutuximab and N-803 significantly enhanced in vitro cytotoxicity of exPBNK with enhanced perforin and IFN-γ release against OS, GBM and NB. The combination of exPBNK+N-803+dinutuximab significantly reduced the secretion of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), platelet-derived growth factor-BB (PDGF-BB), and stem cell growth factor beta (SCGF-β) from OS or GBM tumor cells. Furthermore, OS or GBM significantly inhibited the secretion of regulated on activation, normal T cell expressed and presumably secreted (RANTES) and stromal cell-derived factor-1 alpha (SDF-1α) from exPBNK cells (p<0.001) but significantly enhanced monokine induced by gamma interferon (MIG) secretion from exPBNK cells (p<0.001). N-803 combined with dinutuximab and exPBNK cells significantly extended the survival of OS, GBM or NB xenografted NSG mice.

conclusionsOur results provide the rationale for the development of a clinical trial of N-803 in combination with dinutuximab and ex vivo exPBNK cells in patients with recurrent or metastatic GD2

Indexed as

AnimalsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsHeterograftsHumansImmunotherapyInterleukin-15Killer Cells, NaturalMiceMice, Inbred NODNeoplasmsRecombinant Fusion ProteinsSurvival AnalysisALT-803Antibodies, MonoclonaldinutuximabIL15 protein, humanInterleukin-15Recombinant Fusion ProteinsADCCbrain neoplasmsdinutuximabexpanded natural killer cellsglioblastomaimmunotherapykiller cellsnaturalneuroblastomaosteosarcomasarcomatargeted immunotherapy

Identifiers

PMID34244307
PMCPMC8268924
OpenAlexW3182086608

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.