Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal antibody Fab fragments after administration of avidin.
We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on their potential usefulness as a carrier of neocarzinostatin (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effects of the chA7Fab-NCS immunoconjugate administered to humans. To decrease the kidney accumulation of chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of avidin to nude mice with pancreatic cancer. The accumulation of biotinylated chA7Fab in the blood and the kidneys decreased significantly after the injection of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and kidney accumulation decreased significantly after the injection of avidin. These findings suggest that the injection of biotinylated chA7Fab complexed with NCS followed by avidin may be safer and may permit the administration of larger doses of NCS without the subsequent development of renal failure.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Yamaguchi
T
T
Matsumura
H
H
Yamamoto
K
K
Tsuruta
H
H
Yata
Y
Y
Nishi
H
H
Okamoto
K
K
Kitamura
K
K
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001360:Avidin / Q000494:pharmacology*; D001710:Biotin; D004337:Drug Carriers; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014183:Transplantation, Heterologous; D009353:Zinostatin / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D011993:Recombinant Fusion Proteins; D001360:Avidin; D001710:Biotin; D009353:Zinostatin