Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110.
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-alpha and 230-fold release of IFN-gamma (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.
Witthauer
Juliane
J
Department of Surgery, Grosshadern, University of Munich, Munich, Germany.
Schlereth
Bernd
B
Brischwein
Klaus
K
Winter
Hauke
H
Funke
Ilona
I
Jauch
Karl-Walter
KW
Baeuerle
Patrick
P
Mayer
Barbara
B
D018033:Antibodies, Bispecific / Q000187:drug effects / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D001943:Breast Neoplasms / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D016066:Pleural Effusion, Malignant / Q000276:immunology*; D057127:Single-Chain Antibodies; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000071858:Epithelial Cell Adhesion Molecule; C509173:MT110 monoclonal antibody; D057127:Single-Chain Antibodies