The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

摘要

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.