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Targeting Alpha-Fetoprotein (AFP)–MHC Complex with CAR T-Cell Therapy for Liver Cancer

Overview of attention for article published in Clinical Cancer Research, January 2017
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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 (97th percentile)
  • High Attention Score compared to outputs of the same age and source (98th percentile)

Mentioned by

news
7 news outlets
twitter
51 tweeters
patent
5 patents
facebook
3 Facebook pages

Citations

dimensions_citation
118 Dimensions

Readers on

mendeley
119 Mendeley
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Title
Targeting Alpha-Fetoprotein (AFP)–MHC Complex with CAR T-Cell Therapy for Liver Cancer
Published in
Clinical Cancer Research, January 2017
DOI 10.1158/1078-0432.ccr-16-1203
Pubmed ID
Authors

Hong Liu, Yiyang Xu, Jingyi Xiang, Li Long, Shon Green, Zhiyuan Yang, Bryan Zimdahl, Jingwei Lu, Neal Cheng, Lucas H. Horan, Bin Liu, Su Yan, Pei Wang, Juan Diaz, Lu Jin, Yoko Nakano, Javier F. Morales, Pengbo Zhang, Lian-xing Liu, Binnaz K. Staley, Saul J. Priceman, Christine E. Brown, Stephen J. Forman, Vivien W. Chan, Cheng Liu

Abstract

The majority of tumor-specific antigens are intracellular and/or secreted and therefore previously inaccessible by conventional chimeric antigen receptor (CAR) T cell therapy. Given that all intracellular/secreted proteins are processed into peptides and presented by class I major histocompatibility complexes (MHC) on the surface of tumor cells, we used alpha-fetoprotein (AFP), a specific liver cancer marker, as an example to determine whether peptide-MHC complexes can be targets for CAR T cell therapy against solid tumors. We generated a fully human chimeric antigen receptor, ET1402L1-CAR (AFP-CAR), with exquisite selectivity and specificity for the AFP158-166 peptide complexed with human leukocyte antigen (HLA)-A*02:01. We report that T cells expressing AFP-CAR selectively degranulated, released cytokines, and lysed liver cancer cells that were HLA-A*02:01+/AFP+ while sparing cells from multiple tissue types that were negative for either expressed proteins. In vivo, intratumoral injection of AFP-CAR T cells significantly regressed both Hep G2 and AFP-expressing SK-HEP-1 tumors in SCID-Beige mice (n=8 for each). Moreover, intravenous administration of AFP-CAR T cells in Hep G2 tumor-bearing NSG mice lead to rapid and profound tumor growth inhibition (n=6). Finally, in an established intraperitoneal liver cancer xenograft model, AFP-CAR T cells showed robust anti-tumor activity (n=6). This study demonstrates that CAR T cell immunotherapy targeting intracellular/secreted solid tumor antigens can elicit a potent anti-tumor response. Our approach expands the spectrum of antigens available for redirected T cell therapy against solid malignancies and offers a promising new avenue for liver cancer immunotherapy.

Twitter Demographics

The data shown below were collected from the profiles of 51 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 119 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 119 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 23 19%
Researcher 16 13%
Other 15 13%
Student > Bachelor 12 10%
Student > Master 10 8%
Other 16 13%
Unknown 27 23%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 24 20%
Medicine and Dentistry 20 17%
Agricultural and Biological Sciences 15 13%
Immunology and Microbiology 14 12%
Pharmacology, Toxicology and Pharmaceutical Science 5 4%
Other 15 13%
Unknown 26 22%

Attention Score in Context

This research output has an Altmetric Attention Score of 89. 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 17 May 2022.
All research outputs
#362,542
of 21,366,128 outputs
Outputs from Clinical Cancer Research
#192
of 12,139 outputs
Outputs of similar age
#8,084
of 287,107 outputs
Outputs of similar age from Clinical Cancer Research
#4
of 174 outputs
Altmetric has tracked 21,366,128 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 12,139 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has done particularly well, scoring higher than 98% 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 287,107 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 97% of its contemporaries.
We're also able to compare this research output to 174 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 98% of its contemporaries.