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

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

Research output: Contribution to journalArticle

33 Citations (Scopus)

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 - Jan 1 2005
Externally publishedYes

Fingerprint

Single-Chain Antibodies
Immunoglobulin Fragments
Half-Life
Pharmacokinetics
Immunoglobulin G
Neoplasms

All Science Journal Classification (ASJC) codes

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

Cite this

The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs. / Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Chauhan, Subhash; Colcher, David; Batra, Surinder K.

In: Nuclear Medicine and Biology, Vol. 32, No. 2, 01.01.2005, p. 157-164.

Research output: Contribution to journalArticle

Wittel, Uwe A. ; Jain, Maneesh ; Goel, Apollina ; Chauhan, Subhash ; Colcher, David ; Batra, Surinder K. / The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs. In: Nuclear Medicine and Biology. 2005 ; Vol. 32, No. 2. pp. 157-164.
@article{3050447055c340d5ac2f6e8184d8cc5b,
title = "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.",
author = "Wittel, {Uwe A.} and Maneesh Jain and Apollina Goel and Subhash Chauhan and David Colcher and Batra, {Surinder K.}",
year = "2005",
month = "1",
day = "1",
doi = "10.1016/j.nucmedbio.2004.11.003",
language = "English (US)",
volume = "32",
pages = "157--164",
journal = "Nuclear Medicine and Biology",
issn = "0969-8051",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

AU - Wittel, Uwe A.

AU - Jain, Maneesh

AU - Goel, Apollina

AU - Chauhan, Subhash

AU - Colcher, David

AU - Batra, Surinder K.

PY - 2005/1/1

Y1 - 2005/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=13844310366&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13844310366&partnerID=8YFLogxK

U2 - 10.1016/j.nucmedbio.2004.11.003

DO - 10.1016/j.nucmedbio.2004.11.003

M3 - Article

C2 - 15721761

AN - SCOPUS:13844310366

VL - 32

SP - 157

EP - 164

JO - Nuclear Medicine and Biology

JF - Nuclear Medicine and Biology

SN - 0969-8051

IS - 2

ER -