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A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting

Abstract

A human scFv, 15-9, was selected from a phage display library for binding to murine laminin-1. A diabody was made from the scFv by shortening the linker from 15 to 5 amino acids between the VH and VL sequence. Radioiodinated scFv and diabody were analyzed for size, binding to laminin, and biodistribution in tumor bearing mice. Diabody preparations at concentrations greater than 10 nM were largely dimer forms ({approx}60 kDa) as judged by gel filtration, but diluted diabody was eluted as a monomer ({approx}30 kDa). At low concentrations the radiolabeled diabody did not bind well to laminin. The {sup 125}I diabody had significantly lower accumulation in tumors than did the scFv when injected at lower concentrations. These data indicate that the diabody dimer dissociates at concentrations of about 10 nM resulting in monomers with no binding activity for laminin and poor tumor homing properties.
Authors:
Baocheng, Huang; [1]  Foote, Linda J; [1]  Lankford, Trish K; [1]  Davern, Sandra M; [2]  McKeown, Cathy K; [1]  Kennel, Stephen J [1] 
  1. Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN (United States)
  2. University of Tennessee Medical Research Center, Knoxville, TN (United States)
Publication Date:
Feb 25, 2005
Product Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 327; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2004.12.114; PII: S0006-291X(04)02914-6; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); PBD: 25 Feb 2005
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; BACTERIOPHAGES; GELS; IODINE 125; LABELLED COMPOUNDS; MICE; MONOMERS; NEOPLASMS
OSTI ID:
20619393
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0006-291X; BBRCA9; TRN: US05R1782062898
Submitting Site:
INIS
Size:
page(s) 999-1005
Announcement Date:
Aug 21, 2005

Citation Formats

Baocheng, Huang, Foote, Linda J, Lankford, Trish K, Davern, Sandra M, McKeown, Cathy K, and Kennel, Stephen J. A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting. United States: N. p., 2005. Web. doi:10.1016/j.bbrc.2004.12.114.
Baocheng, Huang, Foote, Linda J, Lankford, Trish K, Davern, Sandra M, McKeown, Cathy K, & Kennel, Stephen J. A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting. United States. https://doi.org/10.1016/j.bbrc.2004.12.114
Baocheng, Huang, Foote, Linda J, Lankford, Trish K, Davern, Sandra M, McKeown, Cathy K, and Kennel, Stephen J. 2005. "A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting." United States. https://doi.org/10.1016/j.bbrc.2004.12.114.
@misc{etde_20619393,
title = {A diabody that dissociates to monomer forms at low concentration: effects on binding activity and tumor targeting}
author = {Baocheng, Huang, Foote, Linda J, Lankford, Trish K, Davern, Sandra M, McKeown, Cathy K, and Kennel, Stephen J}
abstractNote = {A human scFv, 15-9, was selected from a phage display library for binding to murine laminin-1. A diabody was made from the scFv by shortening the linker from 15 to 5 amino acids between the VH and VL sequence. Radioiodinated scFv and diabody were analyzed for size, binding to laminin, and biodistribution in tumor bearing mice. Diabody preparations at concentrations greater than 10 nM were largely dimer forms ({approx}60 kDa) as judged by gel filtration, but diluted diabody was eluted as a monomer ({approx}30 kDa). At low concentrations the radiolabeled diabody did not bind well to laminin. The {sup 125}I diabody had significantly lower accumulation in tumors than did the scFv when injected at lower concentrations. These data indicate that the diabody dimer dissociates at concentrations of about 10 nM resulting in monomers with no binding activity for laminin and poor tumor homing properties.}
doi = {10.1016/j.bbrc.2004.12.114}
journal = []
issue = {4}
volume = {327}
journal type = {AC}
place = {United States}
year = {2005}
month = {Feb}
}