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Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response

Overview of attention for article published in Journal for Immunotherapy of Cancer, November 2017
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (90th percentile)

Mentioned by

news
6 news outlets
twitter
37 tweeters
patent
1 patent

Citations

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77 Dimensions

Readers on

mendeley
162 Mendeley
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Title
Single-cell multiplexed cytokine profiling of CD19 CAR-T cells reveals a diverse landscape of polyfunctional antigen-specific response
Published in
Journal for Immunotherapy of Cancer, November 2017
DOI 10.1186/s40425-017-0293-7
Pubmed ID
Authors

Qiong Xue, Emily Bettini, Patrick Paczkowski, Colin Ng, Alaina Kaiser, Timothy McConnell, Olja Kodrasi, Máire F. Quigley, James Heath, Rong Fan, Sean Mackay, Mark E. Dudley, Sadik H. Kassim, Jing Zhou

Abstract

It remains challenging to characterize the functional attributes of chimeric antigen receptor (CAR)-engineered T cell product targeting CD19 related to potency and immunotoxicity ex vivo, despite promising in vivo efficacy in patients with B cell malignancies. We employed a single-cell, 16-plex cytokine microfluidics device and new analysis techniques to evaluate the functional profile of CD19 CAR-T cells upon antigen-specific stimulation. CAR-T cells were manufactured from human PBMCs transfected with the lentivirus encoding the CD19-BB-z transgene and expanded with anti-CD3/anti-CD28 coated beads. The enriched CAR-T cells were stimulated with anti-CAR or control IgG beads, stained with anti-CD4 RPE and anti-CD8 Alexa Fluor 647 antibodies, and incubated for 16 h in a single-cell barcode chip (SCBC). Each SCBC contains ~12,000 microchambers, covered with a glass slide that was pre-patterned with a complete copy of a 16-plex antibody array. Protein secretions from single CAR-T cells were captured and subsequently analyzed using proprietary software and new visualization methods. We demonstrate a new method for single-cell profiling of CD19 CAR-T pre-infusion products prepared from 4 healthy donors. CAR-T single cells exhibited a marked heterogeneity of cytokine secretions and polyfunctional (2+ cytokine) subsets specific to anti-CAR bead stimulation. The breadth of responses includes anti-tumor effector (Granzyme B, IFN-γ, MIP-1α, TNF-α), stimulatory (GM-CSF, IL-2, IL-8), regulatory (IL-4, IL-13, IL-22), and inflammatory (IL-6, IL-17A) functions. Furthermore, we developed two new bioinformatics tools for more effective polyfunctional subset visualization and comparison between donors. Single-cell, multiplexed, proteomic profiling of CD19 CAR-T product reveals a diverse landscape of immune effector response of CD19 CAR-T cells to antigen-specific challenge, providing a new platform for capturing CAR-T product data for correlative analysis. Additionally, such high dimensional data requires new visualization methods to further define precise polyfunctional response differences in these products. The presented biomarker capture and analysis system provides a more sensitive and comprehensive functional assessment of CAR-T pre-infusion products and may provide insights into the safety and efficacy of CAR-T cell therapy.

Twitter Demographics

The data shown below were collected from the profiles of 37 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 162 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 162 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 39 24%
Researcher 31 19%
Other 15 9%
Student > Bachelor 11 7%
Student > Postgraduate 7 4%
Other 18 11%
Unknown 41 25%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 26 16%
Immunology and Microbiology 22 14%
Agricultural and Biological Sciences 16 10%
Medicine and Dentistry 15 9%
Engineering 13 8%
Other 20 12%
Unknown 50 31%

Attention Score in Context

This research output has an Altmetric Attention Score of 68. 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 23 July 2020.
All research outputs
#473,283
of 21,312,573 outputs
Outputs from Journal for Immunotherapy of Cancer
#102
of 2,568 outputs
Outputs of similar age
#14,554
of 445,072 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#11
of 100 outputs
Altmetric has tracked 21,312,573 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,568 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.2. This one has done particularly well, scoring higher than 96% 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 445,072 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 100 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 90% of its contemporaries.