| Title |
Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma
|
|---|---|
| Published in |
Cancer Immunology, Immunotherapy, May 2017
|
| DOI | 10.1007/s00262-017-2013-z |
| Pubmed ID | |
| Authors |
Roger Gilabert-Oriol, Sebastian G. B. Furness, Brett W. Stringer, Alexander Weng, Hendrik Fuchs, Bryan W. Day, Angela Kourakis, Andrew W. Boyd, David L. Hare, Mayank Thakur, Terrance G. Johns, Peter J. Wookey |
| Abstract |
We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC50 for mAb2C4:dianthin was 10.0 pM and for mAb2C4:MMAE [antibody drug conjugate (ADC)] 2.5 nM, 250-fold less potent. With the cell line U87MG, in the presence of SO1861, the EC50 for mAb2C4:dianthin was 20 pM, mAb2C4:gelonin, 20 pM, compared to the ADC (6.3 nM), which is >300 less potent. Several other HGG cell lines that express CTR were tested and the efficacies of mAb2C4:RIP (dianthin or gelonin) were similar. Co-administration of the enhancer SO1861 purified from plants enhances lysosomal escape. Enhancement with SO1861 increased potency of the immunotoxin (>3 log values) compared to the ADC (1 log). The uptake of antibody was demonstrated with the fluorescent conjugate mAb2C4:Alexa Fluor 568, and the release of dianthin-30:Alexa Fluor488 into the cytosol following addition of SO1861 supports our model. These data demonstrate that the immunotoxins are highly potent and that CTR is an effective target expressed by a large proportion of HGG cell lines representative of glioma stem cells and isolated from individual patients. |
X Demographics
The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 33% |
| Portugal | 1 | 33% |
| Mexico | 1 | 33% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 25 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 25 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 28% |
| Researcher | 5 | 20% |
| Student > Bachelor | 3 | 12% |
| Student > Master | 3 | 12% |
| Lecturer > Senior Lecturer | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 5 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 44% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 12% |
| Medicine and Dentistry | 2 | 8% |
| Neuroscience | 2 | 8% |
| Agricultural and Biological Sciences | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 5 | 20% |
Attention Score in Context
This research output has an Altmetric Attention Score of 15. 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 04 October 2023.
All research outputs
#2,289,471
of 24,167,226 outputs
Outputs from Cancer Immunology, Immunotherapy
#102
of 2,881 outputs
Outputs of similar age
#42,940
of 313,315 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#4
of 43 outputs
Altmetric has tracked 24,167,226 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,881 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one has done particularly well, scoring higher than 96% of its peers.
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