Binding, internalization and the cytotoxicity of monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS) in target cells.
To study the mechanism of action of the monoclonal antibody A7-neocarzinostatin conjugates (A7-NCS), the internalization of the antibody and its conjugate into target cells was examined. The incubation of radiolabeled A7 and A7-NCS with target cells revealed that both were taken up by target cells in a time dependent fashion. The immunocytochemical study using anti-NCS also revealed the intracellular localization of the conjugates. The cytotoxicity of the conjugate was markedly reduced when the binding sites were occupied by an excess of antibody on the cell surface. These results showed that A7-NCS was internalized into target cells and that its cytotoxicity was mediated through specific binding and internalization.
Kitamura
K
K
First Department of Surgery, Kyoto Prefectural University of Medicine.
Takahashi
T
T
Noguchi
A
A
Takashina
K
K
Tsurumi
H
H
Yamaguchi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology; D009353:Zinostatin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009353:Zinostatin