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

Uwe A. Wittel, Maneesh Jain, Apollina Goel, Subhash C. Chauhan, David Colcher, Surinder K. Batra

Research output: Contribution to journalArticle

33 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)157-164
Number of pages8
JournalNuclear Medicine and Biology
Volume32
Issue number2
DOIs
StatePublished - Feb 2005

Keywords

  • Cancer therapy
  • Immunotherapy
  • Monoclonal antibodies
  • Pharmacokinetics

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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