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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Autores principales:	Wei-Chun Chiu, Ya-Ping Lai, Min-Yuan Chou
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4618aec1538484fae9d06c756f68b1c
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spelling	oai:doaj.org-article:e4618aec1538484fae9d06c756f68b1c2021-11-18T06:59:24ZHumanization and characterization of an anti-human TNF-α murine monoclonal antibody.1932-620310.1371/journal.pone.0016373https://doaj.org/article/e4618aec1538484fae9d06c756f68b1c2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21305012/?tool=EBIhttps://doaj.org/toc/1932-6203A 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.Wei-Chun ChiuYa-Ping LaiMin-Yuan ChouPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16373 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wei-Chun Chiu Ya-Ping Lai Min-Yuan Chou Humanization and characterization of an anti-human TNF-α murine monoclonal antibody.
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.
format	article
author	Wei-Chun Chiu Ya-Ping Lai Min-Yuan Chou
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)
publishDate	2011
url	https://doaj.org/article/e4618aec1538484fae9d06c756f68b1c
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Humanization and characterization of an anti-human TNF-α murine monoclonal antibody.

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