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...

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Veröffentlicht in:PloS one 2011-09, Vol.6 (9), p.e23906-e23906
Hauptverfasser: Sidera, Katerina, El Hamidieh, Avraam, Mamalaki, Avgi, Patsavoudi, Evangelia
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El Hamidieh, Avraam
Mamalaki, Avgi
Patsavoudi, Evangelia
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.
doi_str_mv 10.1371/journal.pone.0023906
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immunology</subject><subject>Hsp90 protein</subject><subject>Humans</subject><subject>Hybridomas - cytology</subject><subject>Immunogenicity</subject><subject>Immunoglobulin kappa-Chains - chemistry</subject><subject>Immunoglobulin kappa-Chains - genetics</subject><subject>Immunoglobulin kappa-Chains - metabolism</subject><subject>Immunoglobulin kappa-Chains - pharmacology</subject><subject>Immunoglobulins</subject><subject>In vivo methods and tests</subject><subject>Laboratories</subject><subject>Light</subject><subject>Localization</subject><subject>Lung - drug effects</subject><subject>Lung - pathology</subject><subject>Lung cancer</subject><subject>Lungs</subject><subject>Medicine</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Mice</subject><subject>Molecular Sequence Data</subject><subject>Monoclonal antibodies</subject><subject>Motility</subject><subject>Neoplasm Invasiveness</subject><subject>Neoplasm Metastasis</subject><subject>Permeability</subject><subject>Protein Multimerization</subject><subject>Protein Structure, Quaternary</subject><subject>Proteins</subject><subject>Sequence Analysis, DNA</subject><subject>Single-Chain Antibodies - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sidera, Katerina</au><au>El Hamidieh, Avraam</au><au>Mamalaki, Avgi</au><au>Patsavoudi, Evangelia</au><au>Driscoll, Paul C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The 4C5 cell-impermeable anti-HSP90 antibody with anti-cancer activity, is composed of a single light chain dimer</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>6</volume><issue>9</issue><spage>e23906</spage><epage>e23906</epage><pages>e23906-e23906</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21912649</pmid><doi>10.1371/journal.pone.0023906</doi><tpages>e23906</tpages><oa>free_for_read</oa></addata></record>
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subjects Amino Acid Sequence
Animals
Antibodies, Monoclonal - chemistry
Antibodies, Monoclonal - genetics
Antibodies, Monoclonal - metabolism
Antibodies, Monoclonal - pharmacology
Antibody Specificity
Anticancer properties
Antigens
Antineoplastic Agents - chemistry
Antineoplastic Agents - metabolism
Antineoplastic Agents - pharmacology
Bands
Base Sequence
Biochemistry
Biology
Breast cancer
Cancer
Cancer metastasis
Cancer treatment
Cell Line, Tumor
Cell surface
Chains
Cloning
Cloning, Molecular
E coli
Female
Heat shock proteins
HSP90 Heat-Shock Proteins - immunology
Hsp90 protein
Humans
Hybridomas - cytology
Immunogenicity
Immunoglobulin kappa-Chains - chemistry
Immunoglobulin kappa-Chains - genetics
Immunoglobulin kappa-Chains - metabolism
Immunoglobulin kappa-Chains - pharmacology
Immunoglobulins
In vivo methods and tests
Laboratories
Light
Localization
Lung - drug effects
Lung - pathology
Lung cancer
Lungs
Medicine
Metastases
Metastasis
Mice
Molecular Sequence Data
Monoclonal antibodies
Motility
Neoplasm Invasiveness
Neoplasm Metastasis
Permeability
Protein Multimerization
Protein Structure, Quaternary
Proteins
Sequence Analysis, DNA
Single-Chain Antibodies - chemistry
Single-Chain Antibodies - genetics
Single-Chain Antibodies - metabolism
Single-Chain Antibodies - pharmacology
Tumorigenesis
title The 4C5 cell-impermeable anti-HSP90 antibody with anti-cancer activity, is composed of a single light chain dimer
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