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Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy

Overview of attention for article published in Journal of Experimental & Clinical Cancer Research, April 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (72nd percentile)
  • High Attention Score compared to outputs of the same age and source (82nd percentile)

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2 patents

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Title
Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy
Published in
Journal of Experimental & Clinical Cancer Research, April 2018
DOI 10.1186/s13046-018-0756-9
Pubmed ID
Authors

Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D. Minden, Li Zhang

Abstract

While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. Our results demonstrate the feasibility and benefit of using DNTs as an immunotherapy after the administration of conventional chemotherapy.

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The data shown below were collected from the profiles of 2 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 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 7 16%
Student > Ph. D. Student 6 13%
Researcher 4 9%
Other 3 7%
Lecturer 2 4%
Other 6 13%
Unknown 17 38%
Readers by discipline Count As %
Immunology and Microbiology 8 18%
Biochemistry, Genetics and Molecular Biology 6 13%
Medicine and Dentistry 4 9%
Pharmacology, Toxicology and Pharmaceutical Science 3 7%
Agricultural and Biological Sciences 2 4%
Other 3 7%
Unknown 19 42%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 7. 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 05 October 2022.
All research outputs
#5,167,753
of 25,382,440 outputs
Outputs from Journal of Experimental & Clinical Cancer Research
#299
of 2,382 outputs
Outputs of similar age
#92,622
of 339,945 outputs
Outputs of similar age from Journal of Experimental & Clinical Cancer Research
#6
of 34 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,382 research outputs from this source. They receive a mean Attention Score of 4.8. This one has done well, scoring higher than 87% 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 339,945 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 72% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 82% of its contemporaries.