ALTERED PHARMACOKINETIC AND TUMOR-LOCALIZATION PROPERTIES OF FAB' FRAGMENTS OF A MURINE MONOCLONAL ANTI-CEA ANTIBODY BY COVALENT MODIFICATION WITH LOW-MOLECULAR-WEIGHT DEXTRAN

被引：14

作者：

FAGNANI, R ^{[1
]}

HALPERN, S ^{[1
]}

HAGAN, M ^{[1
]}

机构：

[1] HYBRITECH INC,DIV THERAPEUT,SAN DIEGO,CA 92196

来源：

NUCLEAR MEDICINE COMMUNICATIONS | 1995年 / 16卷 / 05期

关键词：

D O I：

10.1097/00006231-199505000-00008

中图分类号：

R8 [特种医学]; R445 [影像诊断学];

学科分类号：

1002 ; 100207 ; 1009 ;

摘要：

This paper describes the modification of Fab' fragments of ZCE025, a murine monoclonal antibody recognizing carcinoembryonic antigen (CEA), with oxidized dextran of low molecular weight. This modification altered the in vitro and in vivo characteristics of the Fab'. The dextran conjugated fragments exhibited markedly reduced renal uptake and excretion and the prolonged residence time of the Fab' in the vascular compartment. The result was enhanced tumour localization of the derivative compounds compared with underivatized Fab', even though the process of chemical coordination reduced the immunoreactivity of the molecule. The isoelectric point of the molecule was much lower than the unaltered Fab' and previous research has shown this to reduce markedly its potential for inducing a human anti-mouse antibody (HAMA) response. Thus, the conjugation of Fab' fragments with low molecular weight oxidized dextrans can increase the bioavailability of these fragments for tumour localization, while simultaneously reducing their immunogenic potential and renal accumulation problems.

引用

页码：362 / 369

页数：8

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