基因工程改造的二价和四价单链抗体构建体的体内特性
The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs.
作者信息
Wittel Uwe A, Jain Maneesh, Goel Apollina, Chauhan Subhash C, Colcher David, Batra Surinder K
机构信息
Department of Biochemistry and Molecular Biology, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE 68198, USA.
出版信息
Nucl Med Biol. 2005 Feb;32(2):157-64. doi: 10.1016/j.nucmedbio.2004.11.003.
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.
工程化多价单链Fv（scFv）构建体已被证明具有快速的血液清除率和更好的肿瘤穿透性。为了解多价单链抗体片段的血浆半衰期较短的原因，研究了共价二聚体scFv [sc(Fv)2]、非共价四聚体scFv {[sc(Fv)2]2} 和单克隆抗体CC49的IgG的药代动力学特性。scFv在体内显示出形成更高分子聚集体的能力。未观察到共价二聚体接头序列的特异性蛋白水解切割或二聚体scFv非共价缔合形成四价scFv构建体的恶化。总之，sc(Fv)2和[sc(Fv)2]2在体内稳定，在诊断和治疗应用方面具有巨大潜力。
Zotero 插件