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

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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@article{Wittel2005TheIV, title={The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs.}, author={Uwe A. Wittel and Maneesh Rajiv Jain and Apollina Goel and Subhash Chand Chauhan and David M Colcher and Surinder Batra}, journal={Nuclear medicine and biology}, year={2005}, volume={32 2}, pages={157-64} }