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Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial

Overview of attention for article published in Journal for Immunotherapy of Cancer, December 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (89th percentile)
  • Average Attention Score compared to outputs of the same age and source

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Title
Radiotherapy enhances natural killer cell cytotoxicity and localization in pre-clinical canine sarcomas and first-in-dog clinical trial
Published in
Journal for Immunotherapy of Cancer, December 2017
DOI 10.1186/s40425-017-0305-7
Pubmed ID
Authors

Robert J. Canter, Steven K. Grossenbacher, Jennifer A. Foltz, Ian R. Sturgill, Jiwon S. Park, Jesus I. Luna, Michael S. Kent, William T. N. Culp, Mingyi Chen, Jaime F. Modiano, Arta M. Monjazeb, Dean A. Lee, William J. Murphy

Abstract

We have previously shown that radiotherapy (RT) augments natural killer (NK) functions in pre-clinical models of human and mouse cancers, including sarcomas. Since dogs are an excellent outbred model for immunotherapy studies, we sought to assess RT plus local autologous NK transfer in canine sarcomas. Dog NK cells (CD5dim, NKp46+) were isolated from PBMCs and expanded with irradiated K562-C9-mIL21 feeder cells and 100 IU/mL recombinant human IL-2. NK homing and cytotoxicity ± RT were evaluated using canine osteosarcoma tumor lines and dog patient-derived xenografts (PDX). In a first-in-dog clinical trial for spontaneous osteosarcoma, we evaluated RT and intra-tumoral autologous NK transfer. After 14 days, mean NK expansion and yield were 19.0-fold (±8.6) and 258.9(±76.1) ×106 cells, respectively. Post-RT, NK cytotoxicity increased in a dose-dependent fashion in vitro reaching ~ 80% at effector:target ratios of ≥10:1 (P < 0.001). In dog PDX models, allogeneic NK cells were cytotoxic in ex vivo killing assays and produced significant PDX tumor growth delay (P < 0.01) in vivo. After focal RT and intravenous NK transfer, we also observed significantly increased NK homing to tumors in vivo. Of 10 dogs with spontaneous osteosarcoma treated with focal RT and autologous NK transfer, 5 remain metastasis-free at the 6-month primary endpoint with resolution of suspicious pulmonary nodules in one patient. We also observed increased activation of circulating NK cells after treatment and persistence of labelled NK cells in vivo. NK cell homing and cytotoxicity are increased following RT in canine models of sarcoma. Results from a first-in-dog clinical trial are promising, including possible abscopal effects.

X Demographics

X Demographics

The data shown below were collected from the profiles of 34 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 114 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 114 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 16 14%
Other 11 10%
Researcher 11 10%
Student > Bachelor 11 10%
Student > Master 9 8%
Other 24 21%
Unknown 32 28%
Readers by discipline Count As %
Veterinary Science and Veterinary Medicine 19 17%
Medicine and Dentistry 17 15%
Immunology and Microbiology 12 11%
Biochemistry, Genetics and Molecular Biology 9 8%
Agricultural and Biological Sciences 7 6%
Other 9 8%
Unknown 41 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 18. 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 August 2018.
All research outputs
#2,048,539
of 25,382,440 outputs
Outputs from Journal for Immunotherapy of Cancer
#543
of 3,422 outputs
Outputs of similar age
#45,232
of 447,047 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#16
of 32 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,422 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.4. This one has done well, scoring higher than 84% 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 447,047 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 32 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.