Antitumor effect of neocarzinostatin conjugated to human/mouse chimeric Fab fragments of the monoclonal antibody A7 on human pancreatic carcinoma.
The anticancer agent neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of the monoclonal antibody A7 to form the conjugate chA7Fab-NCS. The antitumor effect of chA7Fab-NCS was tested by measuring the inhibition of 3H-thymidine incorporation into human pancreatic carcinoma cells. The chA7Fab-NCS was approximately 2.3 times as effective as free NCS against human pancreatic carcinoma cells which reacted with the monoclonal antibody A7. The antitumor activity of chA7Fab-NCS was inhibited by excess chA7Fab. ChA7Fab-NCS had an antitumor effect equivalent to free NCS on human pancreatic carcinoma cells which did not react with the monoclonal antibody A7. ChA7Fab-NCS appears to be a potentially useful conjugate for immunotargeting chemotherapy against pancreatic carcinoma.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Yamaguchi
T
T
Yata
Y
Y
Nishi
H
H
Okamoto
K
K
Taniguchi
K
K
Kato
M
M
Kotani
T
T
Yamaoka
N
N
Kitamura
K
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D004337:Drug Carriers; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007124:Immunoenzyme Techniques; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D051379:Mice; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D009353:Zinostatin