Evidence map›Paper›PMID 30092835›Full record

ArticleBreast cancer research : BCR2018

Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3) antibodies induced by HER3 vaccines have multiple mechanisms of antitumor activity against therapy resistant and triple negative breast cancers.

Takuya Osada, Zachary C Hartman, Junping Wei, Gangjun Lei, Amy C Hobeika, William R Gwin, Marcio A Diniz, Neil Spector, Timothy M Clay, Wei Chen and 2 more

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

Article in Breast cancer research : BCR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  5. HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022
    Review
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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

12 authors at 5 institutions in 1 country.

Takuya OsadaDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA.
Zachary C HartmanDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA.
Junping WeiDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA.
Gangjun LeiDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA.
Amy C HobeikaDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA.
William R GwinDivision of Medical Oncology, Department of Medicine, University of Washington, Seattle, WA, USA.
Marcio A DinizBiostatistics and Bioinformatics Research Center, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Neil SpectorDivision of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Timothy M ClayCell and Gene Therapy Discovery Research, PTS, GlaxoSmithKline, Collegeville, PA, USA.
Wei ChenDivision of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
Michael A MorseDivision of Medical Oncology, Department of Medicine, Duke University Medical Center, Durham, NC, USA.
H Kim LyerlyDivision of Surgical Sciences, Department of Surgery, Duke University Medical Center, MSRB Research Drive, Box 2714, Durham, NC, 27710, USA. lyerl001@mc.duke.edu.ORCID 0000-0002-0063-4770
Duke Medical Center · USCedars-Sinai Medical Center · USDuke University · USGlaxoSmithKline (United States) · USUniversity of Washington Medical Center · US

Funding

SPORE IN BREAST CANCERP50CA068438 · NCI · DUKE UNIVERSITY · PI LYERLY, HERBERT KIM · 1995 to 2007
$14.3M
Inhibition of Wnt/B-Catenin Signaling in Colorectal Cancer TherapyR01CA172570 · NCI · DUKE UNIVERSITY · PI CHEN, WEI · 2013 to 2017
$1.6M
Redirecting Specificity of Viral Specific T CellsR01CA095447 · NCI · DUKE UNIVERSITY · PI CLAY, TIM · 2003 to 2006
$1.1M
NCI NIH HHS NCI P50 CA89496-01NCI NIH HHS P50 CA068438NCI NIH HHS R01 CA095447NCI NIH HHS R01 CA172570
6 · The paper itself

Abstract

backgroundUpregulation of human epidermal growth factor receptor 3 (HER3) is a major mechanism of acquired resistance to therapies targeting its heterodimerization partners epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for immune attack. We generated an adenovirus encoding full length human HER3 (Ad-HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor efficacy and function of the T cell response to this vaccine. We now provide a detailed assessment of the antitumor efficacy and functional mechanisms of the HER3 vaccine-induced antibodies (HER3-VIAs) in serum from mice immunized with Ad-HER3.

methodsSerum containing HER3-VIA was tested in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) assays and for its effect on HER3 internalization and degradation, downstream signaling of HER3 heterodimers and growth of metastatic HER2+ (BT474M1), HER2 therapy-resistant (rBT474), and triple negative (MDA-MB-468) breast cancers.

resultsHER3-VIAs mediated CDC and ADCC, HER3 internalization, interruption of HER3 heterodimer-driven tumor signaling pathways, and anti-proliferative effects against HER2+ tumor cells in vitro and significant antitumor effects against metastatic HER2+ BT474M1, treatment refractory HER2+ rBT474 and triple negative MDA-MB-468 in vivo.

conclusionsIn addition to the T cell anti-tumor response induced by Ad-HER3, the HER3-VIAs provide additional functions to eliminate tumors in which HER3 signaling mediates aggressive behavior or acquired resistance to HER2-targeted therapy. These data support clinical studies of vaccination against HER3 prior to or concomitantly with other therapies to prevent outgrowth of therapy-resistant HER2+ and triple negative clones.

Indexed as

AdenoviridaeAnimalsAntibodiesAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsBreastCancer VaccinesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmEpitope MappingErb-b2 Receptor Tyrosine KinasesErbB ReceptorsFemaleGenetic VectorsHumansAntibodiesAntineoplastic AgentsCancer VaccinesEGFR protein, humanERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanErbB ReceptorsReceptor, ErbB-3AdenovirusErbB3HER2HER3ImmunotherapyPolyclonal antibodies

Identifiers

PMID30092835
PMCPMC6085609
OpenAlexW2886161066

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.