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Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA–Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy

Overview of attention for article published in Human Gene Therapy, May 2018
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • Good Attention Score compared to outputs of the same age (74th percentile)
  • Average Attention Score compared to outputs of the same age and source

Mentioned by

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9 tweeters

Citations

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10 Dimensions

Readers on

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35 Mendeley
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Title
Development of Anti-Human Mesothelin-Targeted Chimeric Antigen Receptor Messenger RNA–Transfected Peripheral Blood Lymphocytes for Ovarian Cancer Therapy
Published in
Human Gene Therapy, May 2018
DOI 10.1089/hum.2017.080
Pubmed ID
Authors

Chien-Fu Hung, Xuequn Xu, Linhong Li, Ying Ma, Qiu Jin, Angelia Viley, Cornell Allen, Pachai Natarajan, Rama Shivakumar, Madhusudan V. Peshwa, Leisha A. Emens

Abstract

CD19-targeted chimeric antigen receptor (CAR) engineered T/natural kill (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to 'on-target off-tumor' toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK-cells may permit prospective control of 'on-target off-tumor toxicity'. To develop a commercial product for solid tumors, we selected mesothelin as an antigen target based on its association with poor prognosis and over-expression in multiple solid cancers. We hypothesized that selecting, activating, and expanding cells ex vivo prior to mRNA CAR transfection would not be necessary, thus simplifying the complexity and cost of manufacturing. We now report the development of anti-human mesothelin mRNA CAR transfected peripheral blood lymphocytes (CARMA-hMeso), demonstrating the manufacture and cryopreservation of multiple cell aliquots for repeat administration from a single human leukapheresis. We developed a rapid, automated, closed system for cGMP-compliant transfection of mRNA CAR in up to 20 x109 peripheral blood lymphocytes. We show that CARMA-hMeso cells recognize and lyse tumor cells in a mesothelin-specific manner. Expression of CAR was detectable over approximately 7 days in vitro with a progressive decline of CAR expression that appears to correlate with in vitro cell expansion. In a murine ovarian cancer model, a single intra-peritoneal (IP) injection of CARMA-hMeso resulted in the dose-dependent inhibition of tumor growth and improved the survival of mice. Furthermore, repeat weekly IP administrations of the optimal CARMA-hMeso dose further prolonged disease control and survival. No significant off-target toxicities were observed. These data support further investigation of CARMA-hMeso as a potential treatment for ovarian cancer and other solid mesothelin-expressing cancers.

Twitter Demographics

The data shown below were collected from the profiles of 9 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 35 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 35 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 8 23%
Student > Bachelor 6 17%
Student > Ph. D. Student 4 11%
Student > Doctoral Student 3 9%
Student > Master 2 6%
Other 4 11%
Unknown 8 23%
Readers by discipline Count As %
Medicine and Dentistry 9 26%
Biochemistry, Genetics and Molecular Biology 6 17%
Immunology and Microbiology 4 11%
Agricultural and Biological Sciences 3 9%
Engineering 2 6%
Other 1 3%
Unknown 10 29%

Attention Score in Context

This research output has an Altmetric Attention Score of 6. 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 28 May 2018.
All research outputs
#2,893,297
of 12,996,278 outputs
Outputs from Human Gene Therapy
#612
of 2,072 outputs
Outputs of similar age
#89,220
of 345,889 outputs
Outputs of similar age from Human Gene Therapy
#15
of 29 outputs
Altmetric has tracked 12,996,278 research outputs across all sources so far. Compared to these this one has done well and is in the 77th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,072 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has gotten more attention than average, scoring higher than 70% 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 345,889 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 74% of its contemporaries.
We're also able to compare this research output to 29 others from the same source and published within six weeks on either side of this one. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.