Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts.
Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The anti-tumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Yamaguchi
T
T
Tsuruta
H
H
Yata
Y
Y
Nishi
H
H
Okamoto
K
K
Taniguchi
K
K
Kato
M
M
Kotani
T
T
Kitamura
K
K
Takahashi
T
T
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011993:Recombinant Fusion Proteins; D014183:Transplantation, Heterologous; D009353:Zinostatin / Q000008:administration & dosage*
D000888:Antibodies, Anti-Idiotypic; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D009353:Zinostatin