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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…

Overview of attention for article published in Breast Cancer Research, August 2018
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Title
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
Published in
Breast Cancer Research, August 2018
DOI 10.1186/s13058-018-1023-x
Pubmed ID
Authors

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, Michael A. Morse, H. Kim Lyerly

Abstract

Upregulation 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. Serum 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. HER3-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. In 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.

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The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 5 18%
Student > Ph. D. Student 4 14%
Student > Bachelor 3 11%
Lecturer 1 4%
Student > Doctoral Student 1 4%
Other 4 14%
Unknown 10 36%
Readers by discipline Count As %
Medicine and Dentistry 5 18%
Pharmacology, Toxicology and Pharmaceutical Science 2 7%
Biochemistry, Genetics and Molecular Biology 2 7%
Agricultural and Biological Sciences 2 7%
Immunology and Microbiology 2 7%
Other 4 14%
Unknown 11 39%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 20 August 2018.
All research outputs
#20,674,485
of 25,394,764 outputs
Outputs from Breast Cancer Research
#1,708
of 2,054 outputs
Outputs of similar age
#265,242
of 341,456 outputs
Outputs of similar age from Breast Cancer Research
#35
of 39 outputs
Altmetric has tracked 25,394,764 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,054 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.2. This one is in the 8th percentile – i.e., 8% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 341,456 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 12th percentile – i.e., 12% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 39 others from the same source and published within six weeks on either side of this one. This one is in the 7th percentile – i.e., 7% of its contemporaries scored the same or lower than it.