Humanization and characterization of an anti-human TNF-α murine monoclonal antibody.
A murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions...
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2011-01-01
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doaj-e4618aec1538484fae9d06c756f68b1c2021-03-03T19:53:56ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1637310.1371/journal.pone.0016373Humanization and characterization of an anti-human TNF-α murine monoclonal antibody.Wei-Chun ChiuYa-Ping LaiMin-Yuan ChouA murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions were identified via a molecular modeling of m357 built by computer-assisted homology modeling. By replacing these critical surface residues with the human counterparts, a humanized version, h357, was generated. The humanized h357 IgG(1) was then stably expressed in a mammalian cell line and the purified antibody maintained the high antigen binding affinity as compared with the parental m357 based on a soluble TNF-α neutralization bioassay. Furthermore, h357 IgG(1) possesses the ability to mediate antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity upon binding to cells bearing the transmembrane form of TNF-α. In a mouse model of collagen antibody-induced arthritis, h357 IgG significantly inhibited disease progression by intra-peritoneal injection of 50 µg/mouse once-daily for 9 consecutive days. These results provided a basis for the development of h357 IgG as therapeutic use.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21305012/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wei-Chun Chiu Ya-Ping Lai Min-Yuan Chou |
spellingShingle |
Wei-Chun Chiu Ya-Ping Lai Min-Yuan Chou Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. PLoS ONE |
author_facet |
Wei-Chun Chiu Ya-Ping Lai Min-Yuan Chou |
author_sort |
Wei-Chun Chiu |
title |
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. |
title_short |
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. |
title_full |
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. |
title_fullStr |
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. |
title_full_unstemmed |
Humanization and characterization of an anti-human TNF-α murine monoclonal antibody. |
title_sort |
humanization and characterization of an anti-human tnf-α murine monoclonal antibody. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
A murine monoclonal antibody, m357, showing the highly neutralizing activities for human tumor necrosis factor (TNF-α) was chosen to be humanized by a variable domain resurfacing approach. The non-conserved surface residues in the framework regions of both the heavy and light chain variable regions were identified via a molecular modeling of m357 built by computer-assisted homology modeling. By replacing these critical surface residues with the human counterparts, a humanized version, h357, was generated. The humanized h357 IgG(1) was then stably expressed in a mammalian cell line and the purified antibody maintained the high antigen binding affinity as compared with the parental m357 based on a soluble TNF-α neutralization bioassay. Furthermore, h357 IgG(1) possesses the ability to mediate antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity upon binding to cells bearing the transmembrane form of TNF-α. In a mouse model of collagen antibody-induced arthritis, h357 IgG significantly inhibited disease progression by intra-peritoneal injection of 50 µg/mouse once-daily for 9 consecutive days. These results provided a basis for the development of h357 IgG as therapeutic use. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21305012/?tool=EBI |
work_keys_str_mv |
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