Otsuji E, Yamaguchi T, Matsumura H, Yamamoto K, Tsuruta H, Yata Y, Nishi H, Okamoto K, Kitamura K, Takahashi T
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Br J Cancer. 1996 Aug;74(4):597-602. doi: 10.1038/bjc.1996.407.
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.
我们已经研发出单克隆抗体A7（chA7Fab）的嵌合Fab片段，并报道了其作为新制癌菌素（NCS）载体的潜在用途。然而，大量的chA7Fab会在肾脏中蓄积，这可能会导致肾衰竭。这是给予人类的chA7Fab-NCS免疫缀合物的主要副作用之一。为了减少chA7Fab在肾脏中的蓄积，将chA7Fab进行生物素化处理，并随后向患有胰腺癌的裸鼠注射抗生物素蛋白。注射抗生物素蛋白后，生物素化chA7Fab在血液和肾脏中的蓄积显著减少。在一项关于生物素化chA7Fab-NCS的单独实验中，注射抗生物素蛋白后，血液和肾脏中的蓄积也显著减少。这些发现表明，先注射与NCS复合的生物素化chA7Fab，随后注射抗生物素蛋白可能更安全，并且可能允许给予更大剂量的NCS而不会随后出现肾衰竭。
