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Identification of anti-tumour biologics using primary tumour models, 3-D phenotypic screening and image-based multi-parametric profiling

Overview of attention for article published in Molecular Cancer, July 2015
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (86th percentile)

Mentioned by

twitter
4 tweeters
patent
4 patents
googleplus
1 Google+ user

Citations

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43 Dimensions

Readers on

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107 Mendeley
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Title
Identification of anti-tumour biologics using primary tumour models, 3-D phenotypic screening and image-based multi-parametric profiling
Published in
Molecular Cancer, July 2015
DOI 10.1186/s12943-015-0415-0
Pubmed ID
Authors

Alan M. Sandercock, Steven Rust, Sandrine Guillard, Kris F. Sachsenmeier, Nick Holoweckyj, Carl Hay, Matt Flynn, Qihui Huang, Kuan Yan, Bram Herpers, Leo S. Price, Jo Soden, Jim Freeth, Lutz Jermutus, Robert Hollingsworth, Ralph Minter

Abstract

Monolayer cultures of immortalised cell lines are a popular screening tool for novel anti-cancer therapeutics, but these methods can be a poor surrogate for disease states, and there is a need for drug screening platforms which are more predictive of clinical outcome. In this study, we describe a phenotypic antibody screen using three-dimensional cultures of primary cells, and image-based multi-parametric profiling in PC-3 cells, to identify anti-cancer biologics against new therapeutic targets. ScFv Antibodies and designed ankyrin repeat proteins (DARPins) were isolated using phage display selections against primary non-small cell lung carcinoma cells. The selected molecules were screened for anti-proliferative and pro-apoptotic activity against primary cells grown in three-dimensional culture, and in an ultra-high content screen on a 3-D cultured cell line using multi-parametric profiling to detect treatment-induced phenotypic changes. The targets of molecules of interest were identified using a cell-surface membrane protein array. An anti-CUB domain containing protein 1 (CDCP1) antibody was tested for tumour growth inhibition in a patient-derived xenograft model, generated from a stage-IV non-small cell lung carcinoma, with and without cisplatin. Two primary non-small cell lung carcinoma cell models were established for antibody isolation and primary screening in anti-proliferative and apoptosis assays. These assays identified multiple antibodies demonstrating activity in specific culture formats. A subset of the DARPins was profiled in an ultra-high content multi-parametric screen, where 300 morphological features were measured per sample. Machine learning was used to select features to classify treatment responses, then antibodies were characterised based on the phenotypes that they induced. This method co-classified several DARPins that targeted CDCP1 into two sets with different phenotypes. Finally, an anti-CDCP1 antibody significantly enhanced the efficacy of cisplatin in a patient-derived NSCLC xenograft model. Phenotypic profiling using complex 3-D cell cultures steers hit selection towards more relevant in vivo phenotypes, and may shed light on subtle mechanistic variations in drug candidates, enabling data-driven decisions for oncology target validation. CDCP1 was identified as a potential target for cisplatin combination therapy.

Twitter Demographics

The data shown below were collected from the profiles of 4 tweeters 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 107 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 <1%
Netherlands 1 <1%
Unknown 105 98%

Demographic breakdown

Readers by professional status Count As %
Researcher 30 28%
Student > Ph. D. Student 18 17%
Student > Bachelor 9 8%
Other 9 8%
Student > Master 8 7%
Other 13 12%
Unknown 20 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 25 23%
Agricultural and Biological Sciences 20 19%
Medicine and Dentistry 13 12%
Pharmacology, Toxicology and Pharmaceutical Science 6 6%
Immunology and Microbiology 4 4%
Other 12 11%
Unknown 27 25%

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 14 December 2021.
All research outputs
#2,388,529
of 21,321,610 outputs
Outputs from Molecular Cancer
#110
of 1,611 outputs
Outputs of similar age
#32,652
of 247,810 outputs
Outputs of similar age from Molecular Cancer
#1
of 1 outputs
Altmetric has tracked 21,321,610 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,611 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one has done particularly well, scoring higher than 92% of its peers.
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 247,810 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 86% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them