[T-cells activated with a trifunctional bi-specific antibody in head and neck cancer].
BACKGROUND
The trifunctional bi-specific antibody Removab bridges and activates CD3 positive T cells to EpCAM on carcinoma cells and simultaneously binds to an accessory immune cell, thus inducing tumor cell lysis. Following intravenous application, Removab may induce cytokine-related side effects resulting in a sepsis like syndrom. It was questioned, if peripheral mononuclear blood cells (PBMN) already opsonized with Removab could retain antitumor activity and induce less cytokine release than the mere antibody.


METHODS
PBMN of patients with head and neck cancer were incubated with Removab and the released cytokines were washed out. Then the Removab-opsonized PBMN were coincubated with genuine tumor cells of the same patient on a chorioallantois membrane for 24 h (T 24) and 48 h (T 48). Tumor cells coincubated with Cisplatin or solely cell culture medium served as control.


RESULTS
Coincubation of tumor cells with opsonized PBMN resulted in a 32 % decrease of viable cells at T 24 and a 37 % decrease at T 48, whereas viable cells increased by 10 % at T 24 or 3 % at T 48 when incubated with medium alone (p < 0.05). This tumor cytotoxicity was similar to that of Cisplatin (35 % at T 24/37 % at T 48).


CONCLUSIONS
In an autologous human ex vivo tumor system, Removab-opsonized PBMN induce tumor cell lysis with significantly reduced cytokine release after i. v. application.
Gronau
S
S
Hals-Nasen-Ohrenklinik, Universität Ulm. silke.gronau@medizin.uni-ulm.de
Schmitt
M
M
Reinhardt
P
P
Wiesneth
M
M
Riechelmann
H
H
D000328:Adult; D000368:Aged; D000818:Animals; D018033:Antibodies, Bispecific / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017252:CD3 Complex / Q000187:drug effects / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D002642:Chick Embryo; D016207:Cytokines / Q000097:blood*; D003601:Cytotoxicity Tests, Immunologic; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010039:Otorhinolaryngologic Neoplasms / Q000276:immunology*; D011971:Receptors, Immunologic / Q000187:drug effects / Q000276:immunology; D012884:Skin Window Technique; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016207:Cytokines; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D007155:Immunologic Factors; D011971:Receptors, Immunologic; C091196:opsonin receptor