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Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110

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Abstract

In the present study, the efficacy of a new drug, i.e. the bispecific single-chain antibody MT110 targeting the epithelial antigen EpCAM and the T-cell antigen CD3 was tested ex vivo in malignant pleural effusions (MPEs). EpCAM+ epithelial cells were found in 78% of the MPEs (n = 18). Ex vivo treatment of seven MPEs resulted in a dose-dependent specific lysis of 37 ± 27% (±SD) EpCAM+ cells with 10 ng/ml (P = 0.03) and 57 ± 29.5% EpCAM+ cells with 1,000 ng/ml MT110 (P = 0.016) after 72 h. As a prerequisite for redirected lysis, stimulation of the autologous CD4+ and CD8+ cells in MPE by 1,000 ng/ml MT110 resulted in 21 ± 17% CD4+/CD25+ and 29.4 ± 22% CD8+/CD25+ cells (P = 0.016, respectively) after 72 h. This was confirmed by a 22-fold release of TNF-α and 230-fold release of IFN-γ (1,000 ng/ml, 48 h, P = 0.03, respectively). Thus, relapsed breast cancer patients resistant to standard treatment might benefit from targeted therapy using MT110.

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Acknowledgements

The authors thank the Departments of Surgery, Radiology, Gynaecology and Radiotherapy, all located at the University of Munich, Klinikum Großhadern, Munich, Germany for sample collection, Mr. C. Brandl (Micromet AG, Munich, Germany) for technical assistance with the cytokine assays and Dr. A. Crispin (Institute of Biometry and Epidemiology, Munich, Germany) for advice in statistical analysis.

Contributors

Conception and design of the study was done by Barbara Mayer and Bernd Schlereth. Juliane Witthauer processed and analyzed the patient samples, acquired and interpreted the data and performed the statistical analysis. Hauke Winter and Ilona Funke were responsible for the management of the patient samples. Barbara Mayer, Bernd Schlereth, and Klaus Brischwein supervised the study. Karl-Walter Jauch and Patrick Baeuerle were involved in the interpretation of the data. All investigators contributed to the writing of the paper. The study was funded by Micromet and supported by the Curt-Bohnewand-Fonds.

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Authors and Affiliations

  1. Department of Surgery, Großhadern, University of Munich, Munich, Germany

    Juliane Witthauer, Karl-Walter Jauch & Barbara Mayer

  2. Micromet AG, Munich, Germany

    Bernd Schlereth, Klaus Brischwein & Patrick Baeuerle

  3. Zentrum für Pneumologie und Thoraxchirurgie, Asklepios Fachkliniken, Gauting, Munich, Germany

    Hauke Winter

  4. Chirurgische Klinik Dr. Rinecker, Munich, Germany

    Ilona Funke

  5. Department of Surgery, Großhadern, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany

    Barbara Mayer

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  1. Juliane Witthauer
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Correspondence to Barbara Mayer.

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Witthauer, J., Schlereth, B., Brischwein, K. et al. Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110. Breast Cancer Res Treat 117, 471–481 (2009). https://doi.org/10.1007/s10549-008-0185-0

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