Antitumour activity of an immunoconjugate composed of anti-human astrocytoma monoclonal antibody and neocarzinostatin.
Neocarzinostatin (NCS) linked to the thiol group on the hinge region of the Fab' fragment of GA-17, a murine monoclonal antibody reacting with tyrosine-specific phosphorylated antigens, which are exclusively expressed on the cell surface of human astrocytomas, was evaluated for in vivo activity. GA-17-NCS immunoconjugates significantly suppressed the growth of human malignant glioma cell line U87-MG subcutaneous xenografts in nude mice until day 50 when administered intravenously into the tail vein. Disulphide- and thioether-linked GA-17-NCS were nearly equipotent immunoconjugates, but thioether-linked GA-17-NCS was more effective than disulphide-linked conjugates with 250 U/kg NCS content on day 50 (P < 0.05). Thioether-linked GA-17-NCS was significantly more effective on day 50 than free NCS with 500 U/kg or 250 U/kg NCS content (P < 0.05, P < 0.01, respectively). These results suggest that GA-17-NCS may prove useful in the treatment of human malignant gliomas.
Kondo
S
S
Department of Neurosurgery, Utano National Hospital, Kyoto, Japan.
Nakatsu
S
S
Sakahara
H
H
Kobayashi
H
H
Konishi
J
J
Namba
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001254:Astrocytoma / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005910:Glioma / Q000628:therapy*; D000922:Immunotoxins / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D009353:Zinostatin / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D009353:Zinostatin