T-DM1, a novel antibody-drug conjugate, is highly effective against uterine and ovarian carcinosarcomas overexpressing HER2

Roberta Nicoletti, Salvatore Lopez, Stefania Bellone, Emiliano Cocco, Carlton L. Schwab, Jonathan D. Black, Floriana Centritto, Liancheng Zhu, Elena Bonazzoli, Natalia Buza, Pei Hui, Delia Mezzanzanica, Silvana Canevari, Peter E. Schwartz, Thomas J. Rutherford, Alessandro D. Santin

Research output: Contribution to journalArticlepeer-review

Abstract

Ovarian and uterine carcinosarcoma (CS) are characterized by their aggressive clinical behavior and poor prognosis. We evaluated the efficacy of trastuzumab-emtansine (T-DM1), against primary HER2 positive and HER2 negative CS cell lines in vitro and in vivo. Eight primary CS cell lines were evaluated for HER2 amplification and protein expression by fluorescence in situ hybridization, immunohistochemistry, flow cytometry and qRT-PCR. Sensitivity to T-DM1-induced antibody-dependent-cell-mediated-cytotoxicity (ADCC) was evaluated in 4-h-chromium-release-assays. T-DM1 cytostatic and apoptotic activities were evaluated using flow cytometry based proliferation assays. In vivo activity of T-DM1 was also evaluated. HER2 protein overexpression and gene amplification were detected in 25 % (2/8) of the primary CS cell lines. T-DM1 and T were similarly effective in inducing strong ADCC against CS overexpressing HER2 at 3+ levels. In contrast, T-DM1 was dramatically more effective than T in inhibiting cell proliferation (P 

Original languageEnglish
Pages (from-to)29-38
Number of pages10
JournalClinical & Experimental Metastasis
Volume32
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

  • Carcinosarcoma
  • HER2
  • T-DM1
  • Trastuzumab
  • Trastuzumab emtansine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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