Cargando…

The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer

MAb 4C5 is a cell impermeable, anti-HSP90 murine monoclonal antibody, originally produced using hybridoma technology. We have previously shown that mAb 4C5 specifically recognizes both the α- and to a lesser extent the β-isoform of HSP90. Additionally, in vitro and in vivo studies revealed that by s...

Descripción completa

Detalles Bibliográficos
Autores principales: Sidera, Katerina, El Hamidieh, Avraam, Mamalaki, Avgi, Patsavoudi, Evangelia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164667/
https://www.ncbi.nlm.nih.gov/pubmed/21912649
http://dx.doi.org/10.1371/journal.pone.0023906
_version_ 1782211066671923200
author Sidera, Katerina
El Hamidieh, Avraam
Mamalaki, Avgi
Patsavoudi, Evangelia
author_facet Sidera, Katerina
El Hamidieh, Avraam
Mamalaki, Avgi
Patsavoudi, Evangelia
author_sort Sidera, Katerina
collection PubMed
description MAb 4C5 is a cell impermeable, anti-HSP90 murine monoclonal antibody, originally produced using hybridoma technology. We have previously shown that mAb 4C5 specifically recognizes both the α- and to a lesser extent the β-isoform of HSP90. Additionally, in vitro and in vivo studies revealed that by selectively inhibiting the function of cell-surface HSP90, mAb 4C5 significantly impairs cancer cell invasion and metastasis. Here we describe the reconstitution of mAb 4C5 into a mouse-human chimera. More importantly we report that mAb 4C5 and consequently its chimeric counterpart are completely devoid of heavy chain and consist only of a functional kappa light chain dimer. The chimeric antibody is shown to retain the original antibody's specificity and functional properties. Thus it is capable of inhibiting the function of surface HSP90, leading to reduced cancer cell invasion in vitro. Finally, we present in vivo evidence showing that the chimeric 4C5 significantly inhibits the metastatic deposit formation of MDA-MB-453 cells into the lungs of SCID mice. These data suggest that a chimeric kappa light chain antibody could be potentially used as an anti-cancer agent, thereby introducing a novel type of antibody fragment, with reduced possible adverse immunogenic effects, into cancer therapeutics.
format Online
Article
Text
id pubmed-3164667
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-31646672011-09-12 The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer Sidera, Katerina El Hamidieh, Avraam Mamalaki, Avgi Patsavoudi, Evangelia PLoS One Research Article MAb 4C5 is a cell impermeable, anti-HSP90 murine monoclonal antibody, originally produced using hybridoma technology. We have previously shown that mAb 4C5 specifically recognizes both the α- and to a lesser extent the β-isoform of HSP90. Additionally, in vitro and in vivo studies revealed that by selectively inhibiting the function of cell-surface HSP90, mAb 4C5 significantly impairs cancer cell invasion and metastasis. Here we describe the reconstitution of mAb 4C5 into a mouse-human chimera. More importantly we report that mAb 4C5 and consequently its chimeric counterpart are completely devoid of heavy chain and consist only of a functional kappa light chain dimer. The chimeric antibody is shown to retain the original antibody's specificity and functional properties. Thus it is capable of inhibiting the function of surface HSP90, leading to reduced cancer cell invasion in vitro. Finally, we present in vivo evidence showing that the chimeric 4C5 significantly inhibits the metastatic deposit formation of MDA-MB-453 cells into the lungs of SCID mice. These data suggest that a chimeric kappa light chain antibody could be potentially used as an anti-cancer agent, thereby introducing a novel type of antibody fragment, with reduced possible adverse immunogenic effects, into cancer therapeutics. Public Library of Science 2011-09-01 /pmc/articles/PMC3164667/ /pubmed/21912649 http://dx.doi.org/10.1371/journal.pone.0023906 Text en Sidera et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sidera, Katerina
El Hamidieh, Avraam
Mamalaki, Avgi
Patsavoudi, Evangelia
The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title_full The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title_fullStr The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title_full_unstemmed The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title_short The 4C5 Cell-Impermeable Anti-HSP90 Antibody with Anti-Cancer Activity, Is Composed of a Single Light Chain Dimer
title_sort 4c5 cell-impermeable anti-hsp90 antibody with anti-cancer activity, is composed of a single light chain dimer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164667/
https://www.ncbi.nlm.nih.gov/pubmed/21912649
http://dx.doi.org/10.1371/journal.pone.0023906
work_keys_str_mv AT siderakaterina the4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT elhamidiehavraam the4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT mamalakiavgi the4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT patsavoudievangelia the4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT siderakaterina 4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT elhamidiehavraam 4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT mamalakiavgi 4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer
AT patsavoudievangelia 4c5cellimpermeableantihsp90antibodywithanticanceractivityiscomposedofasinglelightchaindimer