Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10916367 | Nuclear Medicine and Biology | 2005 | 8 Pages |
Abstract
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.
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Authors
Uwe A. Wittel, Maneesh Jain, Apollina Goel, Subhash C. Chauhan, David Colcher, Surinder K. Batra,