Academic Journal
T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo
| العنوان: | T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo |
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| المؤلفون: | English, Diana P., Bellone, Stefania, Schwab, Carlton L., Bortolomai, Ileana, Bonazzoli, Elena, Cocco, Emiliano, Buza, Natalia, Hui, Pei, Lopez, Salvatore, Ratner, Elena, Silasi, Dan‐Arin, Azodi, Masoud, Schwartz, Peter E., Rutherford, Thomas J., Santin, Alessandro D. |
| المساهمون: | Honorable Tina Brozman Foundation, Deborah Bunn Alley Ovarian Cancer Research Foundation, National Institutes of Health |
| المصدر: | Cancer Medicine ; volume 3, issue 5, page 1256-1265 ; ISSN 2045-7634 2045-7634 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2014 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | Amplification of c‐erbB2 has been reported in over 30% of uterine serous carcinoma ( USC ) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine ( T‐DM1 ), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor‐2 ( HER 2)‐positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry ( IHC ) and flow cytometry for HER 2 protein expression. C‐erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T‐ DM 1 and trastuzumab (T)‐induced antibody‐dependent cell‐mediated cytotoxicity was evaluated in 5‐h chromium release assays. T‐ DM 1 and T cytostatic and apoptotic activities were evaluated using flow‐cytometry‐based proliferation assays. In vivo activity of T‐ DM 1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER 2 protein overexpression and HER 2 gene amplification were detected in 33% of USC cell lines. T‐ DM 1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis ( P = 0.004) of USC showing HER 2 overexpression. Importantly, T‐ DM 1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER 2 ( P = 0.04) and mice treated with TDM ‐1 had significantly longer survival when compared to T‐treated mice and control mice ( P ≤ 0.0001). T‐ DM 1 shows promising antitumor effect in HER 2‐positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T‐ DM 1 may represent a novel treatment option for HER 2‐positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/cam4.274 |
| الاتاحة: | http://dx.doi.org/10.1002/cam4.274 https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fcam4.274 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cam4.274 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cam4.274 |
| Rights: | http://creativecommons.org/licenses/by/3.0/ |
| رقم الانضمام: | edsbas.B747382 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/cam4.274 |
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