| Title |
Dual B- and T-cell de-immunization of recombinant immunotoxin targeting mesothelin with high cytotoxic activity
|
|---|---|
| Published in |
Oncotarget, May 2016
|
| DOI | 10.18632/oncotarget.9171 |
| Pubmed ID | |
| Authors |
Ronit Mazor, Masanori Onda, Dong Park, Selamawit Addissie, Laiman Xiang, Jingli Zhang, Raffit Hassan, Ira Pastan |
| Abstract |
Recombinant immunotoxins (RITs) are genetically engineered proteins being developed to treat cancer. They are composed of an Fv that targets a cancer antigen and a portion of a protein toxin. Their clinical success is limited by their immunogenicity. Our goal is to produce a new RIT that targets mesothelin and is non-immunogenic by combining mutations that decrease B- and T-cell epitopes. Starting with an immunotoxin that has B-cell epitopes suppressed, we added mutations step-wise that suppress T-cell epitopes. The final protein (LMB-T14) has greatly reduced antigenicity as assessed by binding to human anti-sera and a greatly decreased ability to activate helper T-cells evaluated in a T-cell activation assay. It is very cytotoxic to mesothelioma cells from patients, and to cancer cell lines. LMB-T14 produces complete remissions of a mesothelin expressing cancer (A431/H9) xenograft. The approach used here can be used to de-immunize other therapeutic foreign proteins. |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Korea, Republic of | 1 | 2% |
| Unknown | 48 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 18% |
| Student > Bachelor | 8 | 16% |
| Researcher | 7 | 14% |
| Student > Master | 7 | 14% |
| Student > Postgraduate | 3 | 6% |
| Other | 5 | 10% |
| Unknown | 10 | 20% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 11 | 22% |
| Agricultural and Biological Sciences | 9 | 18% |
| Immunology and Microbiology | 6 | 12% |
| Medicine and Dentistry | 5 | 10% |
| Veterinary Science and Veterinary Medicine | 1 | 2% |
| Other | 3 | 6% |
| Unknown | 14 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 29 October 2020.
All research outputs
#4,804,243
of 23,577,654 outputs
Outputs from Oncotarget
#2,108
of 14,436 outputs
Outputs of similar age
#73,481
of 300,530 outputs
Outputs of similar age from Oncotarget
#135
of 1,314 outputs
Altmetric has tracked 23,577,654 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 14,436 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.8. This one has done well, scoring higher than 84% 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 300,530 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 1,314 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 88% of its contemporaries.