Trifunctional bispecific antibody-induced tumor cell lysis of squamous cell carcinomas of the upper aerodigestive tract.
BACKGROUND
The trifunctional bispecific antibody Removab (tbAB) bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune-cell inducing tumor cell lysis. tbAB-induced tumor cytotoxicity was assessed in an autologous human ex vivo system.


METHODS
One hundred forty tumor samples and autologous peripheral blood mononuclear cells from a total of 36 patients with head and neck squamous cell carcinomas (HNSCCs) were incubated on a chicken embryo chorioallantois membrane with Removab. Tumor cells coincubated with cisplatin or cell culture medium served as positive and negative controls. Tumor cell lysis was assessed by acridine orange staining or by fluorescence-activated cell sorting of propidium iodide-marked cells after 24 and 48 hours (T24/T48) coincubation.


RESULTS
Coincubation of HNSCC cells with tbAB and autologous peripheral blood mononuclear cells resulted in a 49% +/- 6% decrease of viable cells at T24 (p < .005) and in a decrease of 56% +/- 8% at T48 (p < .005) compared with the control. The tumor cytotoxicity was similar to that of cisplatin (49% +/- 7% decrease at T24 and 49% +/- 8% at T48).


CONCLUSIONS
In an autologous human ex vivo system, the tbAB-induced tumor cell lysis was comparable to that by cisplatin.
Gronau
Silke S
SS
Department of Otorhinolaryngology-Head and Neck Surgery, University of Ulm, Prittwitzstr. 43, 89075 Ulm, Germany. silke.gronau@medizin.uni-ulm.de
Schmitt
Michael
M
Thess
Bernard
B
Reinhardt
Peter
P
Wiesneth
Markus
M
Schmitt
Anita
A
Riechelmann
Herbert
H
D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D002945:Cisplatin