| Title |
Targeting HER2/neu with a fully human IgE to harness the allergic reaction against cancer cells
|
|---|---|
| Published in |
Cancer Immunology, Immunotherapy, November 2011
|
| DOI | 10.1007/s00262-011-1150-z |
| Pubmed ID | |
| Authors |
Tracy R. Daniels, Richard K. Leuchter, Rafaela Quintero, Gustavo Helguera, José A. Rodríguez, Otoniel Martínez-Maza, Birgit C. Schultes, Christopher F. Nicodemus, Manuel L. Penichet |
| Abstract |
Breast and ovarian cancer are two of the leading causes of cancer deaths among women in the United States. Overexpression of the HER2/neu oncoprotein has been reported in patients affected with breast and ovarian cancers, and is associated with poor prognosis. To develop a novel targeted therapy for HER2/neu expressing tumors, we have constructed a fully human IgE with the variable regions of the scFv C6MH3-B1 specific for HER2/neu. This antibody was expressed in murine myeloma cells and was properly assembled and secreted. The Fc region of this antibody triggers in vitro degranulation of rat basophilic cells expressing human FcεRI (RBL SX-38) in the presence of murine mammary carcinoma cells that express human HER2/neu (D2F2/E2), but not the shed (soluble) antigen (ECD(HER2)) alone. This IgE is also capable of inducing passive cutaneous anaphylaxis in a human FcεRIα transgenic mouse model, in the presence of a cross-linking antibody, but not in the presence of soluble ECD(HER2). Additionally, IgE enhances antigen presentation in human dendritic cells and facilitates cross-priming, suggesting that the antibody is able to stimulate a secondary T-cell anti-tumor response. Furthermore, we show that this IgE significantly prolongs survival of human FcεRIα transgenic mice bearing D2F2/E2 tumors. We also report that the anti-HER2/neu IgE is well tolerated in a preliminary study conducted in Macaca fascicularis (cynomolgus) monkeys. In summary, our results suggest that this IgE should be further explored as a potential therapeutic against HER2/neu overexpressing tumors, such as breast and ovarian cancers. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Practitioners (doctors, other healthcare professionals) | 1 | 100% |
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 % |
|---|---|---|
| Student > Ph. D. Student | 15 | 43% |
| Researcher | 5 | 14% |
| Student > Bachelor | 5 | 14% |
| Professor > Associate Professor | 3 | 9% |
| Other | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 2 | 6% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 10 | 29% |
| Immunology and Microbiology | 6 | 17% |
| Biochemistry, Genetics and Molecular Biology | 4 | 11% |
| Medicine and Dentistry | 4 | 11% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Other | 4 | 11% |
| Unknown | 5 | 14% |
Attention Score in Context
This research output has an Altmetric Attention Score of 18. 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 13 April 2021.
All research outputs
#1,761,096
of 22,659,164 outputs
Outputs from Cancer Immunology, Immunotherapy
#58
of 2,883 outputs
Outputs of similar age
#13,062
of 239,722 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#3
of 39 outputs
Altmetric has tracked 22,659,164 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 2,883 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. 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 239,722 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 94% of its contemporaries.
We're also able to compare this research output to 39 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 92% of its contemporaries.