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 neocarzinostati n (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effec ts of the chA7Fab-NCS immunoconjugate administered to humans. To decre ase the kidney accumulation of chA7Fab, chA7Fab was biotinylated and a dministered with a subsequent injection of avidin to nude mice with pa ncreatic 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 an d kidney accumulation decreased significantly after the injection of a vidin. These findings suggest that the injection of biotinylated chA7F ab complexed with NCS followed by avidin may be safer and may permit t he administration of larger doses of NCS without the subsequent develo pment of renal failure.