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American Association for Cancer Research

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The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity

Overview of attention for article published in Cancer Immunology Research, September 2014
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (95th percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

Citations

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232 Dimensions

Readers on

mendeley
326 Mendeley
Title
The Nonsignaling Extracellular Spacer Domain of Chimeric Antigen Receptors Is Decisive for In Vivo Antitumor Activity
Published in
Cancer Immunology Research, September 2014
DOI 10.1158/2326-6066.cir-14-0127
Pubmed ID
Authors

Michael Hudecek, Daniel Sommermeyer, Paula L. Kosasih, Anne Silva-Benedict, Lingfeng Liu, Christoph Rader, Michael C. Jensen, Stanley R. Riddell

Abstract

The use of synthetic chimeric antigen receptors (CARs) to redirect T-cells to recognize tumor provides a powerful new approach to cancer immunotherapy, however the attributes of CARs that ensure optimal in vivo tumor recognition remain to be defined. Here, we analyze the influence of length and composition of IgG-derived extracellular spacer domains on the function of CARs. Our studies demonstrate that CD19-CARs with a long spacer from IgG4 hinge-CH2-CH3 are functional in vitro but lack antitumor activity in vivo due to interaction between the Fc domain within the spacer and Fc receptor bearing myeloid cells, leading to activation induced T-cell death. We demonstrate that in vivo persistence and antitumor effects of CAR T-cells with a long spacer can be restored by modifying distinct regions in the CH2 domain that are essential for Fc receptor binding. Our studies demonstrate that modifications that abrogate binding to Fc receptors are crucial for CARs in which a long spacer is obligatory for tumor recognition as shown here for a ROR1-specific CAR. These results demonstrate that the length and composition of the extracellular spacer domain that lacks intrinsic signaling function can be decisive in the design of CARs for optimal in vivo activity.

Twitter Demographics

The data shown below were collected from the profiles of 3 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 326 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 <1%
United Kingdom 1 <1%
Netherlands 1 <1%
Portugal 1 <1%
Unknown 321 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 79 24%
Researcher 71 22%
Student > Master 32 10%
Student > Bachelor 27 8%
Student > Doctoral Student 23 7%
Other 51 16%
Unknown 43 13%
Readers by discipline Count As %
Agricultural and Biological Sciences 80 25%
Immunology and Microbiology 60 18%
Biochemistry, Genetics and Molecular Biology 56 17%
Medicine and Dentistry 48 15%
Engineering 13 4%
Other 22 7%
Unknown 47 14%

Attention Score in Context

This research output has an Altmetric Attention Score of 37. 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 February 2021.
All research outputs
#648,904
of 17,047,319 outputs
Outputs from Cancer Immunology Research
#69
of 1,082 outputs
Outputs of similar age
#8,926
of 208,566 outputs
Outputs of similar age from Cancer Immunology Research
#1
of 31 outputs
Altmetric has tracked 17,047,319 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,082 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 10.0. This one has done particularly well, scoring higher than 93% 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 208,566 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 31 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 99% of its contemporaries.