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Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer

Overview of attention for article published in Journal for Immunotherapy of Cancer, March 2017
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)

Mentioned by

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2 news outlets
twitter
37 tweeters
patent
5 patents

Citations

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150 Dimensions

Readers on

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180 Mendeley
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Title
Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer
Published in
Journal for Immunotherapy of Cancer, March 2017
DOI 10.1186/s40425-017-0222-9
Pubmed ID
Authors

Kristen M. Hege, Emily K. Bergsland, George A. Fisher, John J. Nemunaitis, Robert S. Warren, James G. McArthur, Andy A. Lin, Jeffrey Schlom, Carl H. June, Stephen A. Sherwin

Abstract

T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 10(10) total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72. Fourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had (111)Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed. These findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity.

Twitter Demographics

The data shown below were collected from the profiles of 37 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 180 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 180 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 30 17%
Student > Ph. D. Student 23 13%
Student > Doctoral Student 16 9%
Student > Bachelor 16 9%
Student > Master 15 8%
Other 30 17%
Unknown 50 28%
Readers by discipline Count As %
Medicine and Dentistry 30 17%
Biochemistry, Genetics and Molecular Biology 27 15%
Immunology and Microbiology 20 11%
Agricultural and Biological Sciences 14 8%
Pharmacology, Toxicology and Pharmaceutical Science 9 5%
Other 22 12%
Unknown 58 32%

Attention Score in Context

This research output has an Altmetric Attention Score of 44. 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 30 December 2021.
All research outputs
#741,322
of 21,681,896 outputs
Outputs from Journal for Immunotherapy of Cancer
#164
of 2,679 outputs
Outputs of similar age
#17,183
of 284,269 outputs
Outputs of similar age from Journal for Immunotherapy of Cancer
#1
of 1 outputs
Altmetric has tracked 21,681,896 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 2,679 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.3. 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 284,269 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 93% of its contemporaries.
We're also able to compare this research output to 1 others from the same source and published within six weeks on either side of this one. This one has scored higher than all of them