Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma and a Target for Antibody Drug Conjugates.
Identifieur interne : 000100 ( PubMed/Corpus ); précédent : 000099; suivant : 000101Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma and a Target for Antibody Drug Conjugates.
Auteurs : Laurel M. Schunselaar ; Kim Monkhorst ; Vincent Van Der Noort ; Ruud Wijdeven ; Dennis Peters ; Wilbert Zwart ; Jacques Neefjes ; Paul BaasSource :
- Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer [ 1556-1380 ] ; 2018.
English descriptors
- KwdEn :
- Antibodies, Monoclonal (metabolism), Glycoproteins (metabolism), Humans, Lung Neoplasms (drug therapy), Lung Neoplasms (mortality), Lung Neoplasms (pathology), Mesothelioma (drug therapy), Mesothelioma (mortality), Mesothelioma (pathology), Progression-Free Survival, Survival Analysis, Treatment Outcome, Trophoblasts (metabolism).
- MESH :
- chemical , metabolism : Antibodies, Monoclonal, Glycoproteins.
- drug therapy : Lung Neoplasms, Mesothelioma.
- metabolism : Trophoblasts.
- mortality : Lung Neoplasms, Mesothelioma.
- pathology : Lung Neoplasms, Mesothelioma.
- Humans, Progression-Free Survival, Survival Analysis, Treatment Outcome.
Abstract
The prognosis for patients with mesothelioma is poor, which prompts the need for the development of better treatment options. Antibody drug conjugates (ADCs) are gaining interest as a therapeutic strategy in mesothelioma. Trophoblast glycoprotein (5T4) is an oncofetal protein overexpressed in mesothelioma with low expression in normal tissue and therefore a good candidate for ADC treatment. Here, we evaluated and manipulated 5T4 as a suitable antigen for ADC targeted therapy in patients with mesothelioma.
DOI: 10.1016/j.jtho.2018.06.008
PubMed: 29959059
Links to Exploration step
pubmed:29959059Le document en format XML
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<author><name sortKey="Schunselaar, Laurel M" sort="Schunselaar, Laurel M" uniqKey="Schunselaar L" first="Laurel M" last="Schunselaar">Laurel M. Schunselaar</name>
<affiliation><nlm:affiliation>Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Monkhorst, Kim" sort="Monkhorst, Kim" uniqKey="Monkhorst K" first="Kim" last="Monkhorst">Kim Monkhorst</name>
<affiliation><nlm:affiliation>Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Van Der Noort, Vincent" sort="Van Der Noort, Vincent" uniqKey="Van Der Noort V" first="Vincent" last="Van Der Noort">Vincent Van Der Noort</name>
<affiliation><nlm:affiliation>Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Wijdeven, Ruud" sort="Wijdeven, Ruud" uniqKey="Wijdeven R" first="Ruud" last="Wijdeven">Ruud Wijdeven</name>
<affiliation><nlm:affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Peters, Dennis" sort="Peters, Dennis" uniqKey="Peters D" first="Dennis" last="Peters">Dennis Peters</name>
<affiliation><nlm:affiliation>Core Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Zwart, Wilbert" sort="Zwart, Wilbert" uniqKey="Zwart W" first="Wilbert" last="Zwart">Wilbert Zwart</name>
<affiliation><nlm:affiliation>Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Neefjes, Jacques" sort="Neefjes, Jacques" uniqKey="Neefjes J" first="Jacques" last="Neefjes">Jacques Neefjes</name>
<affiliation><nlm:affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Baas, Paul" sort="Baas, Paul" uniqKey="Baas P" first="Paul" last="Baas">Paul Baas</name>
<affiliation><nlm:affiliation>Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl.</nlm:affiliation>
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<author><name sortKey="Monkhorst, Kim" sort="Monkhorst, Kim" uniqKey="Monkhorst K" first="Kim" last="Monkhorst">Kim Monkhorst</name>
<affiliation><nlm:affiliation>Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Van Der Noort, Vincent" sort="Van Der Noort, Vincent" uniqKey="Van Der Noort V" first="Vincent" last="Van Der Noort">Vincent Van Der Noort</name>
<affiliation><nlm:affiliation>Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Wijdeven, Ruud" sort="Wijdeven, Ruud" uniqKey="Wijdeven R" first="Ruud" last="Wijdeven">Ruud Wijdeven</name>
<affiliation><nlm:affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation>
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<author><name sortKey="Peters, Dennis" sort="Peters, Dennis" uniqKey="Peters D" first="Dennis" last="Peters">Dennis Peters</name>
<affiliation><nlm:affiliation>Core Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
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<author><name sortKey="Zwart, Wilbert" sort="Zwart, Wilbert" uniqKey="Zwart W" first="Wilbert" last="Zwart">Wilbert Zwart</name>
<affiliation><nlm:affiliation>Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Neefjes, Jacques" sort="Neefjes, Jacques" uniqKey="Neefjes J" first="Jacques" last="Neefjes">Jacques Neefjes</name>
<affiliation><nlm:affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation>
</affiliation>
</author>
<author><name sortKey="Baas, Paul" sort="Baas, Paul" uniqKey="Baas P" first="Paul" last="Baas">Paul Baas</name>
<affiliation><nlm:affiliation>Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl.</nlm:affiliation>
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<series><title level="j">Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer</title>
<idno type="eISSN">1556-1380</idno>
<imprint><date when="2018" type="published">2018</date>
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<term>Glycoproteins (metabolism)</term>
<term>Humans</term>
<term>Lung Neoplasms (drug therapy)</term>
<term>Lung Neoplasms (mortality)</term>
<term>Lung Neoplasms (pathology)</term>
<term>Mesothelioma (drug therapy)</term>
<term>Mesothelioma (mortality)</term>
<term>Mesothelioma (pathology)</term>
<term>Progression-Free Survival</term>
<term>Survival Analysis</term>
<term>Treatment Outcome</term>
<term>Trophoblasts (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antibodies, Monoclonal</term>
<term>Glycoproteins</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Lung Neoplasms</term>
<term>Mesothelioma</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Trophoblasts</term>
</keywords>
<keywords scheme="MESH" qualifier="mortality" xml:lang="en"><term>Lung Neoplasms</term>
<term>Mesothelioma</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term>
<term>Mesothelioma</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Humans</term>
<term>Progression-Free Survival</term>
<term>Survival Analysis</term>
<term>Treatment Outcome</term>
</keywords>
</textClass>
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<front><div type="abstract" xml:lang="en">The prognosis for patients with mesothelioma is poor, which prompts the need for the development of better treatment options. Antibody drug conjugates (ADCs) are gaining interest as a therapeutic strategy in mesothelioma. Trophoblast glycoprotein (5T4) is an oncofetal protein overexpressed in mesothelioma with low expression in normal tissue and therefore a good candidate for ADC treatment. Here, we evaluated and manipulated 5T4 as a suitable antigen for ADC targeted therapy in patients with mesothelioma.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">29959059</PMID>
<DateCompleted><Year>2019</Year>
<Month>08</Month>
<Day>29</Day>
</DateCompleted>
<DateRevised><Year>2019</Year>
<Month>08</Month>
<Day>29</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1556-1380</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>13</Volume>
<Issue>10</Issue>
<PubDate><Year>2018</Year>
<Month>10</Month>
</PubDate>
</JournalIssue>
<Title>Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer</Title>
<ISOAbbreviation>J Thorac Oncol</ISOAbbreviation>
</Journal>
<ArticleTitle>Trophoblast Glycoprotein is Associated With a Favorable Outcome for Mesothelioma and a Target for Antibody Drug Conjugates.</ArticleTitle>
<Pagination><MedlinePgn>1577-1587</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S1556-0864(18)30717-2</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.jtho.2018.06.008</ELocationID>
<Abstract><AbstractText Label="INTRODUCTION">The prognosis for patients with mesothelioma is poor, which prompts the need for the development of better treatment options. Antibody drug conjugates (ADCs) are gaining interest as a therapeutic strategy in mesothelioma. Trophoblast glycoprotein (5T4) is an oncofetal protein overexpressed in mesothelioma with low expression in normal tissue and therefore a good candidate for ADC treatment. Here, we evaluated and manipulated 5T4 as a suitable antigen for ADC targeted therapy in patients with mesothelioma.</AbstractText>
<AbstractText Label="METHODS">Expression of the 5T4 antigen is evaluated in (primary) mesothelioma cell lines and biopsy specimens, and correlated with clinical outcome. Internalization was assessed in 5T4 expressing cells. The cytotoxicity of three different 5T4-targeting ADCs was tested on (primary) mesothelioma cells.</AbstractText>
<AbstractText Label="RESULTS">5T4 was expressed in 10 of 12 (primary) cell lines. Most biopsy specimens stained positive for the 5T4 antigen, with marked differences in staining intensity and percentage of positive cells. High expression correlated with long progression-free survival. Both free antibody and ADCs targeting 5T4 were internalized and entered lysosomal compartments. Cytotoxicity experiments showed that cell lines with a high expression for 5T4 were sensitive to two of three ADCs. Lack of efficacy for the third ADC could be restored by neutralizing lysosomal compartments with chloroquine.</AbstractText>
<AbstractText Label="CONCLUSIONS">The 5T4 antigen is expressed in mesothelioma and 5T4-based ADCs are internalized in lysosomes. Two of three ADCs were capable of killing the mesothelioma cells; the third ADC required additional lysosomal neutralization for its effect. 5T4-based ADCs would be a selective strategy for the treatment of mesothelioma.</AbstractText>
<CopyrightInformation>Copyright © 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Schunselaar</LastName>
<ForeName>Laurel M</ForeName>
<Initials>LM</Initials>
<AffiliationInfo><Affiliation>Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Monkhorst</LastName>
<ForeName>Kim</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Department of Pathology, Netherlands Cancer Institute, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van der Noort</LastName>
<ForeName>Vincent</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Biometrics Department, Netherlands Cancer Institute, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wijdeven</LastName>
<ForeName>Ruud</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Peters</LastName>
<ForeName>Dennis</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Core Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zwart</LastName>
<ForeName>Wilbert</ForeName>
<Initials>W</Initials>
<AffiliationInfo><Affiliation>Division of Oncogenomics, Oncode Institute within Netherlands Cancer Institute, Amsterdam, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Neefjes</LastName>
<ForeName>Jacques</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Cell and Chemical Biology, Oncode Institute within Leiden University Medical Center, Leiden, The Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Baas</LastName>
<ForeName>Paul</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. Electronic address: p.baas@nki.nl.</Affiliation>
</AffiliationInfo>
</Author>
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<Language>eng</Language>
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<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
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<Day>27</Day>
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<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>J Thorac Oncol</MedlineTA>
<NlmUniqueID>101274235</NlmUniqueID>
<ISSNLinking>1556-0864</ISSNLinking>
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<SupplMeshList><SupplMeshName Type="Disease" UI="C562839">Mesothelioma, Malignant</SupplMeshName>
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<MeshHeadingList><MeshHeading><DescriptorName UI="D000911" MajorTopicYN="N">Antibodies, Monoclonal</DescriptorName>
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<MeshHeading><DescriptorName UI="D006023" MajorTopicYN="N">Glycoproteins</DescriptorName>
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</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
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<MeshHeading><DescriptorName UI="D008175" MajorTopicYN="N">Lung Neoplasms</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
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<MeshHeading><DescriptorName UI="D008654" MajorTopicYN="N">Mesothelioma</DescriptorName>
<QualifierName UI="Q000188" MajorTopicYN="Y">drug therapy</QualifierName>
<QualifierName UI="Q000401" MajorTopicYN="N">mortality</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000077982" MajorTopicYN="N">Progression-Free Survival</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016019" MajorTopicYN="N">Survival Analysis</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016896" MajorTopicYN="N">Treatment Outcome</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D014327" MajorTopicYN="N">Trophoblasts</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">5T4</Keyword>
<Keyword MajorTopicYN="Y">Antibody-drug conjugate</Keyword>
<Keyword MajorTopicYN="Y">Lysosome</Keyword>
<Keyword MajorTopicYN="Y">Malignant pleural mesothelioma</Keyword>
<Keyword MajorTopicYN="Y">treatment</Keyword>
</KeywordList>
</MedlineCitation>
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