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

Juliane Witthauer (1) , Bernd Schlereth (2) , Klaus Brischwein (2) , Hauke Winter (3) , Ilona Funke (4) , Karl-Walter Jauch (1) , Patrick Baeuerle (2) , Barbara Mayer (1, 5)

1 Department of Surgery, Großhadern
2 Micromet AG
3 Zentrum für Pneumologie und Thoraxchirurgie
4 Chirurgische Klinik Dr. Rinecker
5 Department of Surgery, Großhadern

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 ( = 18). Ex vivo treatment of seven MPEs resulted in a dose-dependent specific lysis of 37 ± 27% (±SD) EpCAM cells with 10 ng/ml ( = 0.03) and 57 ± 29.5% EpCAM cells with 1,000 ng/ml MT110 ( = 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 ( = 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,  = 0.03, respectively). Thus, relapsed breast cancer patients resistant to standard treatment might benefit from targeted therapy using MT110.

Mots clés: Malignant pleural effusion; Breast cancer; Bispecific antibody; EpCAM; CD3; MT110; Ex vivo therapy

Juliane Witthauer, Bernd Schlereth, Klaus Brischwein, Hauke Winter, Ilona Funke, et al.. Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110. Breast Cancer Research and Treatment, 2008, 117 (3), pp.471-481. ⟨10.1007/s10549-008-0185-0⟩. ⟨hal-00478266⟩