부산대학교 도서관

Byline: 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) Keywords: Malignant pleural effusion; Breast cancer; Bispecific antibody; EpCAM; CD3; MT110; Ex vivo therapy 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.sup.+ 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.sup.+ cells with 10 ng/ml (P = 0.03) and 57 +- 29.5% EpCAM.sup.+ cells with 1,000 ng/ml MT110 (P = 0.016) after 72 h. As a prerequisite for redirected lysis, stimulation of the autologous CD4.sup.+ and CD8.sup.+ cells in MPE by 1,000 ng/ml MT110 resulted in 21 +- 17% CD4.sup.+/CD25.sup.+ and 29.4 +- 22% CD8.sup.+/CD25.sup.+ cells (P = 0.016, respectively) after 72 h. This was confirmed by a 22-fold release of TNF-[alpha] and 230-fold release of IFN-I3 (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. Author Affiliation: (1) Department of Surgery, Grosshadern, University of Munich, Munich, Germany (2) Micromet AG, Munich, Germany (3) Zentrum fur Pneumologie und Thoraxchirurgie, Asklepios Fachkliniken, Gauting, Munich, Germany (4) Chirurgische Klinik Dr. Rinecker, Munich, Germany (5) Department of Surgery, Grosshadern, Ludwig-Maximilians-University, Marchioninistr. 15, 81377, Munich, Germany Article History: Registration Date: 04/09/2008 Received Date: 07/07/2008 Accepted Date: 03/09/2008 Online Date: 26/09/2008