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Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models

Overview of attention for article published in Breast Cancer Research, September 2018
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Title
Evaluation of anti-PD-1-based therapy against triple-negative breast cancer patient-derived xenograft tumors engrafted in humanized mouse models
Published in
Breast Cancer Research, September 2018
DOI 10.1186/s13058-018-1037-4
Pubmed ID
Authors

Roberto R. Rosato, Daniel Dávila-González, Dong Soon Choi, Wei Qian, Wen Chen, Anthony J. Kozielski, Helen Wong, Bhuvanesh Dave, Jenny C. Chang

Abstract

Breast cancer has been considered not highly immunogenic, and few patients benefit from current immunotherapies. However, new strategies are aimed at changing this paradigm. In the present study, we examined the in vivo activity of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor models. To circumvent some of the limitations posed by the lack of appropriate animal models in preclinical studies of immunotherapies, partially human leukocyte antigen-matched TNBC PDX tumor lines from our collection, as well as human melanoma cell lines, were engrafted in humanized nonobese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice obtained by intravenous injection of CD34+ hematopoietic stem cells into nonlethally irradiated 3-4-week-old mice. After both PDXs and melanoma cell xenografts reached ~ 150-200 mm3, animals were treated with humanized anti-PD-1 antibody or anti-CTLA-4 and evaluated for tumor growth, survival, and potential mechanism of action. Human CD45+, CD20+, CD3+, CD8+, CD56+, CD68+, and CD33+ cells were readily identified in blood, spleen, and bone marrow collected from hNSG, as well as human cytokines in blood and engrafted tumors. Engraftment of TNBC PDXs in hNSG was high (~ 85%), although they grew at a slightly slower pace and conserved their ability to generate lung metastasis. Human CD45+ cells were detectable in hNSG-harbored PDXs, and consistent with clinical observations, anti-PD-1 antibody therapy resulted in both a significant reduction in tumor growth and increased survival in some of the hNSG PDX tumor lines, whereas no such effects were observed in the corresponding non-hNSG models. This study provides evidence associated with anti-PD-1 immunotherapy against TNBC tumors supporting the use of TNBC PDXs in humanized mice as a model to overcome some of the technical difficulties associated with the preclinical investigation of immune-based therapies.

Twitter Demographics

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

Mendeley readers

The data shown below were compiled from readership statistics for 106 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 106 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 23 22%
Student > Ph. D. Student 19 18%
Student > Bachelor 9 8%
Student > Master 7 7%
Student > Postgraduate 6 6%
Other 17 16%
Unknown 25 24%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 27 25%
Medicine and Dentistry 20 19%
Agricultural and Biological Sciences 7 7%
Immunology and Microbiology 7 7%
Pharmacology, Toxicology and Pharmaceutical Science 6 6%
Other 6 6%
Unknown 33 31%

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 07 September 2018.
All research outputs
#11,952,505
of 13,480,923 outputs
Outputs from Breast Cancer Research
#1,384
of 1,515 outputs
Outputs of similar age
#228,676
of 265,281 outputs
Outputs of similar age from Breast Cancer Research
#2
of 2 outputs
Altmetric has tracked 13,480,923 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,515 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 10.0. This one is in the 1st percentile – i.e., 1% 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 265,281 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 2 others from the same source and published within six weeks on either side of this one.