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Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab

Overview of attention for article published in Journal for Immunotherapy of Cancer, August 2015
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  • Good Attention Score compared to outputs of the same age (74th percentile)

Mentioned by

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5 tweeters
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2 patents

Citations

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43 Dimensions

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78 Mendeley
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Title
Characterization of the human T cell response to in vitro CD27 costimulation with varlilumab
Published in
Journal for Immunotherapy of Cancer, August 2015
DOI 10.1186/s40425-015-0080-2
Pubmed ID
Authors

Venky Ramakrishna, Karuna Sundarapandiyan, Biwei Zhao, Max Bylesjo, Henry C. Marsh, Tibor Keler

Abstract

Clinical targeting of TNFR family of receptors (CD40, CD134 and CD137) with immunostimulatory monoclonal antibodies has been successful in cancer immunotherapy. However, targeting of CD27 with a mAb is a relatively new approach to provide costimulation of immune cells undergoing activation. Thus, activation of human CD27 (TNFRSF7) with a monoclonal antibody (varlilumab) has previously been demonstrated to result in T cell activation and anti-tumor activity in preclinical models, and is currently in early phase clinical trials in patients with advanced malignancies. In this study we used an in vitro system using human peripheral blood T cells to characterize the varlilumab-mediated costimulatory effects in combination with TCR stimulation in terms of phenotypic, transcriptional and functionality changes. T cells were isolated from normal volunteer PBMCs using magnetic bead isolation kits and stimulated in vitro with plate bound anti-CD3 Ab (OKT3) and varlilumab or control Ab for 72 h. Activation profiles were monitored by ELISA or Luminex-based testing cytokine/chemokine releases, cell surface phenotyping for costimulatory and coinhibitory markers and CFSE dye dilution by proliferating T cells and Tregs. Changes in gene expression and transcriptome analysis of varlilumab-stimulated T cells was carried on Agilent Human whole genome microarray datasets using a suite of statistical and bioinformatic software tools. Costimulation of T cells with varlilumab required continuous TCR signaling as pre-activated T cells were unable to produce cytokines with CD27 signaling alone. Analysis of T cell subsets further revealed that memory CD4+ and CD8+ T cells were specifically activated with a bias toward CD8+ T lymphocyte proliferation. Activation was accompanied by upregulated cell surface expression of costimulatory [4-1BB, OX40, GITR and ICOS] and coinhibitory [PD-1] molecules. Importantly, varlilumab costimulation did not activate purified Tregs as measured by cytokine production, proliferation and suppression of dividing non-Treg T cells. Analysis of changes in gene expression during varlilumab stimulation of T cells revealed modulation of pro-inflammatory signatures consistent with cellular activation and proliferation, with the IL-2 pathway showing the highest frequency of gene modulation. Altogether, the data reveal the requirements and T cell subtype-specific effects of CD27 costimulation, and helps select relevant biomarkers for studying the effects of varlilumab in patients.

Twitter Demographics

The data shown below were collected from the profiles of 5 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 78 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Spain 1 1%
Unknown 77 99%

Demographic breakdown

Readers by professional status Count As %
Researcher 19 24%
Student > Ph. D. Student 12 15%
Student > Master 10 13%
Student > Bachelor 9 12%
Other 6 8%
Other 10 13%
Unknown 12 15%
Readers by discipline Count As %
Immunology and Microbiology 17 22%
Agricultural and Biological Sciences 17 22%
Biochemistry, Genetics and Molecular Biology 15 19%
Medicine and Dentistry 7 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 4%
Other 5 6%
Unknown 14 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 5. 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 10 October 2019.
All research outputs
#4,586,726
of 17,358,590 outputs
Outputs from Journal for Immunotherapy of Cancer
#746
of 1,743 outputs
Outputs of similar age
#61,846
of 244,280 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 1 outputs
Altmetric has tracked 17,358,590 research outputs across all sources so far. This one has received more attention than most of these and is in the 73rd percentile.
So far Altmetric has tracked 1,743 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 13.7. This one has gotten more attention than average, scoring higher than 56% 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 244,280 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 74% 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