Evidence map›Paper›PMID 30898149›Full record

ArticleJournal for immunotherapy of cancer2019

Mechanisms involved in IL-15 superagonist enhancement of anti-PD-L1 therapy.

Karin M Knudson, Kristin C Hicks, Sarah Alter, Jeffrey Schlom, Sofia R Gameiro

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04294576 (First-in-human), which is not on this map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
5.9field-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.

NCT04294576 phase1unknown statusnot on this map

First-in-human (FIH), Open-Label, Phase 1a (Dose Escalation)/Phase 1b (Expansion Cohort) Trial of BJ-001 as a Single Agent and in Combination With Pembrolizumab in Patients With Locally Advanced/Metastatic Solid Tumors

TypeinterventionalSponsorBJ Bioscience, Inc.Ran2019 to 2024Enrolled92ConditionsLocally Advanced/Metastatic Solid TumorsArmsBJ-001, Pembrolizumab
3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 111 citations in OpenAlex.

  1. Trial
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  5. Article
  6. Epigenetic plus cytokine therapy induces stem-like CD8Journal for immunotherapy of cancer · 2026
    Article
  7. Dynamics changes of spleen volume predict survival outcomes in unresectable hepatocellular carcinoma treated with tislelizumab plus lenvatinib.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Article
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  15. Function ofEJNMMI reports · 2025
    Article
  16. Concurrent intratumoural TNature biomedical engineering · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Review

22 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

5 authors at 2 institutions in 2 countries.

Karin M KnudsonLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Kristin C HicksLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Sarah AlterAltor Bioscience, a NantWorks company, Miramar, FL, USA.
Jeffrey SchlomLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. js141c@nih.gov.ORCID 0000-0001-7932-4072
Sofia R GameiroLaboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USBioscience (China) · CN

Funding

Strategies for Cancer Vaccine Development: Preclinical StudiesZIABC010944 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SCHLOM, JEFFREY · 2009 to 2025
$26.6M
6 · The paper itself

Abstract

backgroundImmunotherapy targeting PD-1/PD-L1 fails to induce clinical responses in most patients with solid cancers. N-803, formerly ALT-803, is an IL-15 superagonist mutant and dimeric IL-15RαSushi-Fc fusion protein complex that enhances CD8

methodsSubcutaneous N-803 and an anti-PD-L1 monoclonal antibody were administered as monotherapy or in combination to 4T1 triple negative breast and MC38-CEA colon tumor-bearing mice. Anti-tumor efficacy was evaluated, and a comprehensive analysis of the immune-mediated effects of each therapy was performed on the primary tumor, lung as a site of metastasis, and spleen.

resultsWe demonstrate that N-803 treatment increased PD-L1 expression on immune cells in vivo, supporting the combination of N-803 and anti-PD-L1. N-803 plus anti-PD-L1 was well-tolerated, reduced 4T1 lung metastasis and MC38-CEA tumor burden, and increased survival as compared to N-803 and anti-PD-L1 monotherapies. Efficacy of the combination therapy was dependent on both CD8

conclusionsWe provide novel insight into the mechanism of action of N-803 plus anti-PD-L1 combination and offer preclinical proof of concept supporting clinical use of N-803 in combination with checkpoint inhibitors, including for patients non- and/or minimally responsive to either monotherapy.

Indexed as

AnimalsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCD8-Positive T-LymphocytesCell Line, TumorColonic NeoplasmsDrug SynergismFemaleHumansInjections, SubcutaneousKiller Cells, NaturalMiceProteinsRecombinant Fusion ProteinsTreatment OutcomeALT-803Antibodies, MonoclonalB7-H1 AntigenProteinsRecombinant Fusion ProteinsALT-803N-803PD-L1Tumor microenvironment

Identifiers

PMID30898149
PMCPMC6429734
OpenAlexW2940611353

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.