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Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules

Overview of attention for article published in Journal of Translational Medicine, January 2018
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4 tweeters

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9 Dimensions

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48 Mendeley
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Title
Enhanced clinical-scale manufacturing of TCR transduced T-cells using closed culture system modules
Published in
Journal of Translational Medicine, January 2018
DOI 10.1186/s12967-018-1384-z
Pubmed ID
Authors

Jianjian Jin, Nikolaos Gkitsas, Vicki S. Fellowes, Jiaqiang Ren, Steven A. Feldman, Christian S. Hinrichs, David F. Stroncek, Steven L. Highfill

Abstract

Genetic engineering of T-cells to express specific T cell receptors (TCR) has emerged as a novel strategy to treat various malignancies. More widespread utilization of these types of therapies has been somewhat constrained by the lack of closed culture processes capable of expanding sufficient numbers of T-cells for clinical application. Here, we evaluate a process for robust clinical grade manufacturing of TCR gene engineered T-cells. TCRs that target human papillomavirus E6 and E7 were independently tested. A 21 day process was divided into a transduction phase (7 days) and a rapid expansion phase (14 days). This process was evaluated using two healthy donor samples and four samples obtained from patients with epithelial cancers. The process resulted in ~ 2000-fold increase in viable nucleated cells and high transduction efficiencies (64-92%). At the end of culture, functional assays demonstrated that these cells were potent and specific in their ability to kill tumor cells bearing target and secrete large quantities of interferon and tumor necrosis factor. Both phases of culture were contained within closed or semi-closed modules, which include automated density gradient separation and cell culture bags for the first phase and closed GREX culture devices and wash/concentrate systems for the second phase. Large-scale manufacturing using modular systems and semi-automated devices resulted in highly functional clinical-grade TCR transduced T-cells. This process is now in use in actively accruing clinical trials and the NIH Clinical Center and can be utilized at other cell therapy manufacturing sites that wish to scale-up and optimize their processing using closed systems.

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 48 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 48 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 12 25%
Student > Ph. D. Student 8 17%
Student > Master 7 15%
Unspecified 6 13%
Other 6 13%
Other 9 19%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 12 25%
Unspecified 10 21%
Medicine and Dentistry 7 15%
Agricultural and Biological Sciences 6 13%
Engineering 4 8%
Other 9 19%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 11 June 2018.
All research outputs
#7,597,045
of 13,184,891 outputs
Outputs from Journal of Translational Medicine
#1,117
of 2,610 outputs
Outputs of similar age
#168,150
of 347,172 outputs
Outputs of similar age from Journal of Translational Medicine
#2
of 3 outputs
Altmetric has tracked 13,184,891 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,610 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.1. This one has gotten more attention than average, scoring higher than 50% 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 347,172 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 3 others from the same source and published within six weeks on either side of this one.