Title |
Mesothelin, a novel immunotherapy target for triple negative breast cancer
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Published in |
Breast Cancer Research and Treatment, March 2012
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DOI | 10.1007/s10549-012-2018-4 |
Pubmed ID | |
Authors |
Julia Tchou, Liang-Chuan Wang, Ben Selven, Hongtao Zhang, Jose Conejo-Garcia, Hossein Borghaei, Michael Kalos, Robert H. Vondeheide, Steven M. Albelda, Carl H. June, Paul J. Zhang |
Abstract |
Mesothelin is a cell-surface glycoprotein present on mesothelial cells and elicits T cell responses in a variety of cancers including pancreatic, biliary and ovarian cancer. Breast cancer is not known to express mesothelin. We postulated that mesothelin may be a unique tumor-associated antigen in triple negative breast cancer (TNBC), a less common breast cancer subtype which may have been under-represented in prior studies that characterized mesothelin expression. Therefore, we screened 99 primary breast cancer samples by immunohistochemistry analysis using formalin-fixed paraffin-embedded archival tumor tissues and confirmed that mesothelin was overexpressed in the majority of TNBC (67 %) but only rarely in <5 % ER(+) or Her2-neu(+) breast cancer, respectively. To determine whether mesothelin may be exploited as a novel immunotherapy target in breast cancer, an in vitro cell killing assay was performed to compare the ability of genetically modified T cells expressing a chimeric antibody receptor (CAR) specific for mesothelin (mesoCAR T cells) or non-transduced T cells to kill mesothelin-expressing primary breast cancer cells. A significantly higher anti-tumor cytotoxicity by mesoCAR T cells was observed (31.7 vs. 8.7 %, p < 0.001). Our results suggest that mesothelin has promise as a novel immunotherapy target for TNBC for which effective targeted therapy is lacking to date. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Romania | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Practitioners (doctors, other healthcare professionals) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 2 | 2% |
Unknown | 120 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 19 | 16% |
Researcher | 17 | 14% |
Student > Bachelor | 14 | 11% |
Professor > Associate Professor | 13 | 11% |
Student > Master | 13 | 11% |
Other | 25 | 20% |
Unknown | 21 | 17% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 24 | 20% |
Biochemistry, Genetics and Molecular Biology | 23 | 19% |
Agricultural and Biological Sciences | 21 | 17% |
Immunology and Microbiology | 19 | 16% |
Chemistry | 3 | 2% |
Other | 9 | 7% |
Unknown | 23 | 19% |