Decreased renal accumulation of biotinylated chimeric monoclonal antibody-neocarzinostatin conjugate after administration of avidin.
Murine monoclonal antibodies (mAbs) such as A7 administered to humans induce a human anti-mouse antibody response. Moreover, because Fab fragments of mAbs are able to penetrate target tumors easily, they may be more suitable than intact mAb to be carriers of anticancer agents such as neocarzinostatin (NCS), which are rapidly inactivated in the blood. To address these problems, chimeric A7 Fab fragment-NCS conjugate (chA7Fab-NCS) was produced. However, large amounts of 125I-labeled chA7Fab-NCS accumulate in the kidney and can lead to renal dysfunction. To decrease renal accumulation of chA7Fab-NCS, chA7Fab was biotinylated and administered with a subsequent injection of avidin. Human pancreatic carcinoma-bearing nude mice were injected with 125I-labeled biotinylated chA7Fab-NCS with or without subsequent administration of avidin. The accumulation of 125I-labeled biotinylated chA7Fab-NCS in tissue samples was measured at appropriate time intervals. 125I-labeled biotinylated chA7Fab-NCS was cleared more rapidly from the blood and the kidney with the administration of avidin than without it. There was no difference between tumor accumulation in these groups. The tumor/blood ratio of radioactivity of 125I-labeled biotinylated chA7Fab-NCS was significantly higher with subsequent administration of avidin than without avidin. The administration of biotinylated chA7Fab-NCS followed by avidin may enhance safety and permit the administration of larger doses of NCS without the subsequent development of renal failure. A larger amount of 125I-labeled biotinylated chA7Fab-NCS was retained in the liver and spleen with the subsequent administration of avidin than without avidin.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine.
Yamaguchi
T
T
Yamamoto
K
K
Matsumura
H
H
Tsuruta
H
H
Yata
Y
Y
Nishi
H
H
Okamoto
K
K
Kitamura
K
K
Takahashi
T
T
D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D000922:Immunotoxins / Q000378:metabolism*; D007457:Iodine Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D010190:Pancreatic Neoplasms / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D019809:Streptavidin; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D007140:Immunoglobulin Fab Fragments; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D001710:Biotin; D019809:Streptavidin; D009353:Zinostatin