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Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts

Overview of attention for article published in Journal for Immunotherapy of Cancer, December 2013
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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 (89th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

Mentioned by

patent
8 patents

Citations

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89 Dimensions

Readers on

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88 Mendeley
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Title
Expression of miR-17-92 enhances anti-tumor activity of T-cells transduced with the anti-EGFRvIII chimeric antigen receptor in mice bearing human GBM xenografts
Published in
Journal for Immunotherapy of Cancer, December 2013
DOI 10.1186/2051-1426-1-21
Pubmed ID
Authors

Masasuke Ohno, Takayuki Ohkuri, Akemi Kosaka, Kuniaki Tanahashi, Carl H June, Atsushi Natsume, Hideho Okada

Abstract

Expression of miR-17-92 enhances T-cell survival and interferon (IFN)-γ production. We previously reported that miR-17-92 is down-regulated in T-cells derived from glioblastoma (GBM) patients. We hypothesized that transgene-derived co-expression of miR17-92 and chimeric antigen receptor (CAR) in T-cells would improve the efficacy of adoptive transfer therapy against GBM. We constructed novel lentiviral vectors for miR-17-92 (FG12-EF1a-miR-17/92) and a CAR consisting of an epidermal growth factor receptor variant III (EGFRvIII)-specific, single-chain variable fragment (scFv) coupled to the T-cell receptor CD3ζ chain signaling module and co-stimulatory motifs of CD137 (4-1BB) and CD28 in tandem (pELNS-3C10-CAR). Human T-cells were transduced with these lentiviral vectors, and their anti-tumor effects were evaluated both in vitro and in vivo. CAR-transduced T-cells (CAR-T-cells) exhibited potent, antigen-specific, cytotoxic activity against U87 GBM cells that stably express EGFRvIII (U87-EGFRvIII) and, when co-transduced with miR-17-92, exhibited improved survival in the presence of temozolomide (TMZ) compared with CAR-T-cells without miR-17-92 co-transduction. In mice bearing intracranial U87-EGFRvIII xenografts, CAR-T-cells with or without transgene-derived miR-17-92 expression demonstrated similar levels of therapeutic effect without demonstrating any uncontrolled growth of CAR-T-cells. However, when these mice were re-challenged with U87-EGFRvIII cells in their brains, mice receiving co-transduced CAR-T-cells exhibited improved protection compared with mice treated with CAR-T-cells without miR-17-92 co-transduction. These results warrant the development of novel CAR-T-cell strategies that incorporate miR-17-92 to improve therapeutic potency, especially in patients with GBM.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 88 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Japan 1 1%
United States 1 1%
Germany 1 1%
Switzerland 1 1%
Unknown 84 95%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 19 22%
Researcher 19 22%
Student > Master 11 13%
Student > Bachelor 8 9%
Student > Doctoral Student 6 7%
Other 10 11%
Unknown 15 17%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 24%
Biochemistry, Genetics and Molecular Biology 20 23%
Medicine and Dentistry 14 16%
Immunology and Microbiology 6 7%
Pharmacology, Toxicology and Pharmaceutical Science 3 3%
Other 8 9%
Unknown 16 18%
Attention Score in Context

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 06 September 2023.
All research outputs
#2,943,926
of 25,918,104 outputs
Outputs from Journal for Immunotherapy of Cancer
#818
of 3,485 outputs
Outputs of similar age
#32,659
of 325,993 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#3
of 62 outputs
Altmetric has tracked 25,918,104 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 3,485 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.6. This one has done well, scoring higher than 76% 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 325,993 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 89% of its contemporaries.
We're also able to compare this research output to 62 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 93% of its contemporaries.