The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs
The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs
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DOI：
10.1016/j.nucmedbio.2004.11.003
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发表时间：
2005-02-01
影响因子：
3.1
通讯作者：
Batra, SK
中科院分区：
文献类型：
--
作者：
Wittel, UA;Jain, M;Batra, SK
工程化的多价单链Fv（scFv）构建体已被证明表现出快速的血液清除和更好的肿瘤穿透。为了理解多价单链抗体片段的短血浆半衰期，检查了MAb CC 49的共价二聚体scFv [sc（FV）（2）]、非共价四聚体scFv {[sc（FV）（2）]（2）}和IgG的药代动力学性质。scFv显示出在体内形成更高分子聚集体的能力。未观察到共价二聚体的接头序列的特异性蛋白水解切割或二聚体scFv非共价结合成四价scFv构建体的劣化。总之，sc（FV）2和[sc（FV）（2）]（2）在体内是稳定的，并且具有诊断和治疗应用的显著潜力。(c)2005年爱思唯尔公司All rights reserved.
Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(FV)(2)], noncovalent tetrameric scFv {[sc(FV)(2)](2)} and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(FV)2 and [sc(FV)(2)](2) are stable in vivo and have significant potential for diagnostic and therapeutic applications. (c) 2005 Elsevier Inc. All rights reserved.