Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
Identifieur interne : 000A22 ( Istex/Corpus ); précédent : 000A21; suivant : 000A23Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
Auteurs : Ashley J. Knights ; Natko Nuber ; Christopher W. Thomson ; Olga De La Rosa ; Elke J Ger ; Jean-Marie Tiercy ; Maries Van Den Broek ; Steve Pascolo ; Alexander Knuth ; Alfred ZippeliusSource :
- Cancer Immunology, Immunotherapy [ 0340-7004 ] ; 2009-03-01.
English descriptors
Abstract
Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.
Url:
DOI: 10.1007/s00262-008-0556-8
Links to Exploration step
ISTEX:FB348E966C97B26FE3CAD53DCCFDA28764096FFCLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title><author><name sortKey="Knights, Ashley J" sort="Knights, Ashley J" uniqKey="Knights A" first="Ashley J." last="Knights">Ashley J. Knights</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ashley.knights@usz.ch</mods:affiliation></affiliation></author><author><name sortKey="Nuber, Natko" sort="Nuber, Natko" uniqKey="Nuber N" first="Natko" last="Nuber">Natko Nuber</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Thomson, Christopher W" sort="Thomson, Christopher W" uniqKey="Thomson C" first="Christopher W." last="Thomson">Christopher W. Thomson</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="De La Rosa, Olga" sort="De La Rosa, Olga" uniqKey="De La Rosa O" first="Olga" last="De La Rosa">Olga De La Rosa</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="J Ger, Elke" sort="J Ger, Elke" uniqKey="J Ger E" first="Elke" last="J Ger">Elke J Ger</name><affiliation><mods:affiliation>Krankenhaus Nordwest, Frankfurt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Tiercy, Jean Marie" sort="Tiercy, Jean Marie" uniqKey="Tiercy J" first="Jean-Marie" last="Tiercy">Jean-Marie Tiercy</name><affiliation><mods:affiliation>University Hospital, Geneva, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Van Den Broek, Maries" sort="Van Den Broek, Maries" uniqKey="Van Den Broek M" first="Maries" last="Van Den Broek">Maries Van Den Broek</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Pascolo, Steve" sort="Pascolo, Steve" uniqKey="Pascolo S" first="Steve" last="Pascolo">Steve Pascolo</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Knuth, Alexander" sort="Knuth, Alexander" uniqKey="Knuth A" first="Alexander" last="Knuth">Alexander Knuth</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Zippelius, Alfred" sort="Zippelius, Alfred" uniqKey="Zippelius A" first="Alfred" last="Zippelius">Alfred Zippelius</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital Basel, Basel, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: Azippelius@uhbs.ch</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:FB348E966C97B26FE3CAD53DCCFDA28764096FFC</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1007/s00262-008-0556-8</idno><idno type="url">https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">000A22</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000A22</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title><author><name sortKey="Knights, Ashley J" sort="Knights, Ashley J" uniqKey="Knights A" first="Ashley J." last="Knights">Ashley J. Knights</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: ashley.knights@usz.ch</mods:affiliation></affiliation></author><author><name sortKey="Nuber, Natko" sort="Nuber, Natko" uniqKey="Nuber N" first="Natko" last="Nuber">Natko Nuber</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Thomson, Christopher W" sort="Thomson, Christopher W" uniqKey="Thomson C" first="Christopher W." last="Thomson">Christopher W. Thomson</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="De La Rosa, Olga" sort="De La Rosa, Olga" uniqKey="De La Rosa O" first="Olga" last="De La Rosa">Olga De La Rosa</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="J Ger, Elke" sort="J Ger, Elke" uniqKey="J Ger E" first="Elke" last="J Ger">Elke J Ger</name><affiliation><mods:affiliation>Krankenhaus Nordwest, Frankfurt, Germany</mods:affiliation></affiliation></author><author><name sortKey="Tiercy, Jean Marie" sort="Tiercy, Jean Marie" uniqKey="Tiercy J" first="Jean-Marie" last="Tiercy">Jean-Marie Tiercy</name><affiliation><mods:affiliation>University Hospital, Geneva, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Van Den Broek, Maries" sort="Van Den Broek, Maries" uniqKey="Van Den Broek M" first="Maries" last="Van Den Broek">Maries Van Den Broek</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Pascolo, Steve" sort="Pascolo, Steve" uniqKey="Pascolo S" first="Steve" last="Pascolo">Steve Pascolo</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Knuth, Alexander" sort="Knuth, Alexander" uniqKey="Knuth A" first="Alexander" last="Knuth">Alexander Knuth</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation></author><author><name sortKey="Zippelius, Alfred" sort="Zippelius, Alfred" uniqKey="Zippelius A" first="Alfred" last="Zippelius">Alfred Zippelius</name><affiliation><mods:affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>University Hospital Basel, Basel, Switzerland</mods:affiliation></affiliation><affiliation><mods:affiliation>E-mail: Azippelius@uhbs.ch</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Cancer Immunology, Immunotherapy</title><title level="j" type="abbrev">Cancer Immunol Immunother</title><idno type="ISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2009-03-01">2009-03-01</date><biblScope unit="volume">58</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="325">325</biblScope><biblScope unit="page" to="338">338</biblScope></imprint><idno type="ISSN">0340-7004</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0340-7004</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Antigens/peptides/epitopes</term><term>T cells</term><term>Tumour immunity</term><term>Vaccination</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</div></front></TEI><istex><corpusName>springer-journals</corpusName><author><json:item><name>Ashley J. Knights</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string><json:string>E-mail: ashley.knights@usz.ch</json:string></affiliations></json:item><json:item><name>Natko Nuber</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Christopher W. Thomson</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Olga de la Rosa</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Elke Jäger</name><affiliations><json:string>Krankenhaus Nordwest, Frankfurt, Germany</json:string></affiliations></json:item><json:item><name>Jean-Marie Tiercy</name><affiliations><json:string>University Hospital, Geneva, Switzerland</json:string></affiliations></json:item><json:item><name>Maries van den Broek</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Steve Pascolo</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Alexander Knuth</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string></affiliations></json:item><json:item><name>Alfred Zippelius</name><affiliations><json:string>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</json:string><json:string>University Hospital Basel, Basel, Switzerland</json:string><json:string>E-mail: Azippelius@uhbs.ch</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>T cells</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Tumour immunity</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Vaccination</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>Antigens/peptides/epitopes</value></json:item></subject><articleId><json:string>556</json:string><json:string>s00262-008-0556-8</json:string></articleId><arkIstex>ark:/67375/VQC-L7000B3R-5</arkIstex><language><json:string>eng</json:string></language><originalGenre><json:string>OriginalPaper</json:string></originalGenre><abstract>Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</abstract><qualityIndicators><score>9.94</score><pdfWordCount>8134</pdfWordCount><pdfCharCount>51259</pdfCharCount><pdfVersion>1.3</pdfVersion><pdfPageCount>14</pdfPageCount><pdfPageSize>595 x 791 pts</pdfPageSize><refBibsNative>false</refBibsNative><abstractWordCount>245</abstractWordCount><abstractCharCount>1738</abstractCharCount><keywordCount>4</keywordCount></qualityIndicators><title>Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title><genre><json:string>research-article</json:string></genre><host><title>Cancer Immunology, Immunotherapy</title><language><json:string>unknown</json:string></language><publicationDate>2009</publicationDate><copyrightDate>2009</copyrightDate><issn><json:string>0340-7004</json:string></issn><eissn><json:string>1432-0851</json:string></eissn><journalId><json:string>262</json:string></journalId><volume>58</volume><issue>3</issue><pages><first>325</first><last>338</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>Cancer Research</value></json:item><json:item><value>Oncology</value></json:item><json:item><value>Immunology</value></json:item></subject></host><ark><json:string>ark:/67375/VQC-L7000B3R-5</json:string></ark><publicationDate>2009</publicationDate><copyrightDate>2008</copyrightDate><doi><json:string>10.1007/s00262-008-0556-8</json:string></doi><id>FB348E966C97B26FE3CAD53DCCFDA28764096FFC</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher scheme="https://scientific-publisher.data.istex.fr">Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><availability><licence><p>Springer-Verlag, 2008</p></licence><p scheme="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</p></availability><date>2008-05-26</date></publicationStmt><notesStmt><note type="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="journal" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note><note>Original Article</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title><author xml:id="author-0000" corresp="yes"><persName><forename type="first">Ashley</forename><surname>Knights</surname></persName><email>ashley.knights@usz.ch</email><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0001"><persName><forename type="first">Natko</forename><surname>Nuber</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0002"><persName><forename type="first">Christopher</forename><surname>Thomson</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0003"><persName><forename type="first">Olga</forename><surname>de la Rosa</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0004"><persName><forename type="first">Elke</forename><surname>Jäger</surname></persName><affiliation>Krankenhaus Nordwest, Frankfurt, Germany</affiliation></author><author xml:id="author-0005"><persName><forename type="first">Jean-Marie</forename><surname>Tiercy</surname></persName><affiliation>University Hospital, Geneva, Switzerland</affiliation></author><author xml:id="author-0006"><persName><forename type="first">Maries</forename><surname>van den Broek</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0007"><persName><forename type="first">Steve</forename><surname>Pascolo</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0008"><persName><forename type="first">Alexander</forename><surname>Knuth</surname></persName><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation></author><author xml:id="author-0009" corresp="yes"><persName><forename type="first">Alfred</forename><surname>Zippelius</surname></persName><email>Azippelius@uhbs.ch</email><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><affiliation>University Hospital Basel, Basel, Switzerland</affiliation></author><idno type="istex">FB348E966C97B26FE3CAD53DCCFDA28764096FFC</idno><idno type="ark">ark:/67375/VQC-L7000B3R-5</idno><idno type="DOI">10.1007/s00262-008-0556-8</idno><idno type="article-id">556</idno><idno type="article-id">s00262-008-0556-8</idno></analytic><monogr><title level="j">Cancer Immunology, Immunotherapy</title><title level="j" type="abbrev">Cancer Immunol Immunother</title><idno type="pISSN">0340-7004</idno><idno type="eISSN">1432-0851</idno><idno type="journal-ID">true</idno><idno type="issue-article-count">15</idno><idno type="volume-issue-count">12</idno><imprint><publisher>Springer-Verlag</publisher><pubPlace>Berlin/Heidelberg</pubPlace><date type="published" when="2009-03-01"></date><biblScope unit="volume">58</biblScope><biblScope unit="issue">3</biblScope><biblScope unit="page" from="325">325</biblScope><biblScope unit="page" to="338">338</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2008-05-26</date></creation><langUsage><language ident="en">en</language></langUsage><abstract xml:lang="en"><p>Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>Keywords</head><item><term>T cells</term></item><item><term>Tumour immunity</term></item><item><term>Vaccination</term></item><item><term>Antigens/peptides/epitopes</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>Biomedicine</head><item><term>Cancer Research</term></item><item><term>Oncology</term></item><item><term>Immunology</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2008-05-26">Created</change><change when="2009-03-01">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus springer-journals not found" wicri:toSee="no header"><istex:xmlDeclaration>version="1.0" encoding="UTF-8"</istex:xmlDeclaration><istex:docType PUBLIC="-//Springer-Verlag//DTD A++ V2.4//EN" URI="http://devel.springer.de/A++/V2.4/DTD/A++V2.4.dtd" name="istex:docType"></istex:docType><istex:document><Publisher><PublisherInfo><PublisherName>Springer-Verlag</PublisherName><PublisherLocation>Berlin/Heidelberg</PublisherLocation></PublisherInfo><Journal OutputMedium="All"><JournalInfo JournalProductType="ArchiveJournal" NumberingStyle="Unnumbered"><JournalID>262</JournalID><JournalPrintISSN>0340-7004</JournalPrintISSN><JournalElectronicISSN>1432-0851</JournalElectronicISSN><JournalTitle>Cancer Immunology, Immunotherapy</JournalTitle><JournalAbbreviatedTitle>Cancer Immunol Immunother</JournalAbbreviatedTitle><JournalSubjectGroup><JournalSubject Type="Primary">Biomedicine</JournalSubject><JournalSubject Type="Secondary">Cancer Research </JournalSubject><JournalSubject Type="Secondary">Oncology </JournalSubject><JournalSubject Type="Secondary">Immunology</JournalSubject></JournalSubjectGroup></JournalInfo><Volume OutputMedium="All"><VolumeInfo TocLevels="0" VolumeType="Regular"><VolumeIDStart>58</VolumeIDStart><VolumeIDEnd>58</VolumeIDEnd><VolumeIssueCount>12</VolumeIssueCount></VolumeInfo><Issue IssueType="Regular" OutputMedium="All"><IssueInfo IssueType="Regular" TocLevels="0"><IssueIDStart>3</IssueIDStart><IssueIDEnd>3</IssueIDEnd><IssueArticleCount>15</IssueArticleCount><IssueHistory><OnlineDate><Year>2009</Year><Month>1</Month><Day>6</Day></OnlineDate><PrintDate><Year>2009</Year><Month>1</Month><Day>5</Day></PrintDate><CoverDate><Year>2009</Year><Month>3</Month></CoverDate><PricelistYear>2009</PricelistYear></IssueHistory><IssueCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName><CopyrightYear>2009</CopyrightYear></IssueCopyright></IssueInfo><Article ID="s00262-008-0556-8" OutputMedium="All"><ArticleInfo ArticleType="OriginalPaper" ContainsESM="No" Language="En" NumberingStyle="Unnumbered" TocLevels="0"><ArticleID>556</ArticleID><ArticleDOI>10.1007/s00262-008-0556-8</ArticleDOI><ArticleSequenceNumber>2</ArticleSequenceNumber><ArticleTitle Language="En" OutputMedium="All">Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</ArticleTitle><ArticleCategory>Original Article</ArticleCategory><ArticleFirstPage>325</ArticleFirstPage><ArticleLastPage>338</ArticleLastPage><ArticleHistory><RegistrationDate><Year>2008</Year><Month>6</Month><Day>26</Day></RegistrationDate><Received><Year>2008</Year><Month>5</Month><Day>26</Day></Received><Accepted><Year>2008</Year><Month>6</Month><Day>25</Day></Accepted><OnlineDate><Year>2008</Year><Month>7</Month><Day>29</Day></OnlineDate></ArticleHistory><ArticleCopyright><CopyrightHolderName>Springer-Verlag</CopyrightHolderName><CopyrightYear>2008</CopyrightYear></ArticleCopyright><ArticleGrants Type="Regular"><MetadataGrant Grant="OpenAccess"></MetadataGrant><AbstractGrant Grant="OpenAccess"></AbstractGrant><BodyPDFGrant Grant="Restricted"></BodyPDFGrant><BodyHTMLGrant Grant="Restricted"></BodyHTMLGrant><BibliographyGrant Grant="Restricted"></BibliographyGrant><ESMGrant Grant="Restricted"></ESMGrant></ArticleGrants></ArticleInfo><ArticleHeader><AuthorGroup><Author AffiliationIDS="Aff1" CorrespondingAffiliationID="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Ashley</GivenName><GivenName>J.</GivenName><FamilyName>Knights</FamilyName></AuthorName><Contact><Email>ashley.knights@usz.ch</Email></Contact></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Natko</GivenName><FamilyName>Nuber</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Christopher</GivenName><GivenName>W.</GivenName><FamilyName>Thomson</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Olga</GivenName><Particle>de</Particle><FamilyName>la Rosa</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff2"><AuthorName DisplayOrder="Western"><GivenName>Elke</GivenName><FamilyName>Jäger</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff3"><AuthorName DisplayOrder="Western"><GivenName>Jean-Marie</GivenName><FamilyName>Tiercy</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Maries</GivenName><Particle>van</Particle><FamilyName>den Broek</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Steve</GivenName><FamilyName>Pascolo</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1"><AuthorName DisplayOrder="Western"><GivenName>Alexander</GivenName><FamilyName>Knuth</FamilyName></AuthorName></Author><Author AffiliationIDS="Aff1 Aff4" CorrespondingAffiliationID="Aff4" PresentAffiliationID="Aff4"><AuthorName DisplayOrder="Western"><GivenName>Alfred</GivenName><FamilyName>Zippelius</FamilyName></AuthorName><Contact><Email>Azippelius@uhbs.ch</Email></Contact></Author><Affiliation ID="Aff1"><OrgDivision>Medical Oncology, Department of Internal Medicine</OrgDivision><OrgName>University Hospital Zurich</OrgName><OrgAddress><Street>Rämistrasse 100</Street><Postcode>8091</Postcode><City>Zurich</City><Country Code="CH">Switzerland</Country></OrgAddress></Affiliation><Affiliation ID="Aff2"><OrgName>Krankenhaus Nordwest</OrgName><OrgAddress><City>Frankfurt</City><Country Code="DE">Germany</Country></OrgAddress></Affiliation><Affiliation ID="Aff3"><OrgName>University Hospital</OrgName><OrgAddress><City>Geneva</City><Country Code="CH">Switzerland</Country></OrgAddress></Affiliation><Affiliation ID="Aff4"><OrgName>University Hospital Basel</OrgName><OrgAddress><City>Basel</City><Country Code="CH">Switzerland</Country></OrgAddress></Affiliation></AuthorGroup><Abstract ID="Abs1" Language="En" OutputMedium="All"><Heading>Abstract</Heading><Para>The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</Para></Abstract><KeywordGroup Language="En" OutputMedium="All"><Heading>Keywords</Heading><Keyword>T cells</Keyword><Keyword>Tumour immunity</Keyword><Keyword>Vaccination</Keyword><Keyword>Antigens/peptides/epitopes</Keyword></KeywordGroup></ArticleHeader><NoBody></NoBody></Article></Issue></Volume></Journal></Publisher></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients</title></titleInfo><name type="personal" displayLabel="corresp"><namePart type="given">Ashley</namePart><namePart type="given">J.</namePart><namePart type="family">Knights</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><affiliation>E-mail: ashley.knights@usz.ch</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Natko</namePart><namePart type="family">Nuber</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Christopher</namePart><namePart type="given">W.</namePart><namePart type="family">Thomson</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Olga</namePart><namePart type="family">de la Rosa</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Elke</namePart><namePart type="family">Jäger</namePart><affiliation>Krankenhaus Nordwest, Frankfurt, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jean-Marie</namePart><namePart type="family">Tiercy</namePart><affiliation>University Hospital, Geneva, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Maries</namePart><namePart type="family">van den Broek</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Steve</namePart><namePart type="family">Pascolo</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Alexander</namePart><namePart type="family">Knuth</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal" displayLabel="corresp"><namePart type="given">Alfred</namePart><namePart type="family">Zippelius</namePart><affiliation>Medical Oncology, Department of Internal Medicine, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland</affiliation><affiliation>University Hospital Basel, Basel, Switzerland</affiliation><affiliation>E-mail: Azippelius@uhbs.ch</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="OriginalPaper" authority="ISTEX" authorityURI="https://content-type.data.istex.fr" valueURI="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</genre><originInfo><publisher>Springer-Verlag</publisher><place><placeTerm type="text">Berlin/Heidelberg</placeTerm></place><dateCreated encoding="w3cdtf">2008-05-26</dateCreated><dateIssued encoding="w3cdtf">2009-03-01</dateIssued><copyrightDate encoding="w3cdtf">2008</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><abstract lang="en">Abstract: The development of effective anti-cancer vaccines requires precise assessment of vaccine-induced immunity. This is often hampered by low ex vivo frequencies of antigen-specific T cells and limited defined epitopes. This study investigates the applicability of modified, in vitro-transcribed mRNA encoding a therapeutically relevant tumour antigen to analyse T cell responses in cancer patients. In this study transfection of antigen presenting cells, by mRNA encoding the tumour antigen NY-ESO-1, was optimised and applied to address spontaneous and vaccine-induced T cell responses in cancer patients. Memory CD8+ T cells from lung cancer patients having detectable humoral immune responses directed towards NY-ESO-1 could be efficiently detected in peripheral blood. Specific T cells utilised a range of different T cell receptors, indicating a polyclonal response. Specific killing of a panel of NY-ESO-1 expressing tumour cell lines indicates recognition restricted to several HLA allelic variants, including a novel HLA-B49 epitope. Using a modified mRNA construct targeting the translated antigen to the secretory pathway, detection of NY-ESO-1-specific CD4+ T cells in patients could be enhanced, which allowed the in-depth characterisation of established T cell clones. Moreover, broad CD8+ and CD4+ T cell responses covering multiple epitopes were detected following mRNA stimulation of patients treated with a recombinant vaccinia/fowlpox NY-ESO-1 vaccine. This approach allows for a precise monitoring of responses to tumour antigens in a setting that addresses the breadth and magnitude of antigen-specific T cell responses, and that is not limited to a particular combination of known epitopes and HLA-restrictions.</abstract><note>Original Article</note><subject lang="en"><genre>Keywords</genre><topic>T cells</topic><topic>Tumour immunity</topic><topic>Vaccination</topic><topic>Antigens/peptides/epitopes</topic></subject><relatedItem type="host"><titleInfo><title>Cancer Immunology, Immunotherapy</title></titleInfo><titleInfo type="abbreviated"><title>Cancer Immunol Immunother</title></titleInfo><genre type="journal" authority="ISTEX" authorityURI="https://publication-type.data.istex.fr" valueURI="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</genre><originInfo><publisher>Springer</publisher><dateIssued encoding="w3cdtf">2009-01-06</dateIssued><copyrightDate encoding="w3cdtf">2009</copyrightDate></originInfo><subject><genre>Biomedicine</genre><topic>Cancer Research</topic><topic>Oncology</topic><topic>Immunology</topic></subject><identifier type="ISSN">0340-7004</identifier><identifier type="eISSN">1432-0851</identifier><identifier type="JournalID">262</identifier><identifier type="IssueArticleCount">15</identifier><identifier type="VolumeIssueCount">12</identifier><part><date>2009</date><detail type="volume"><number>58</number><caption>vol.</caption></detail><detail type="issue"><number>3</number><caption>no.</caption></detail><extent unit="pages"><start>325</start><end>338</end></extent></part><recordInfo><recordOrigin>Springer-Verlag, 2009</recordOrigin></recordInfo></relatedItem><identifier type="istex">FB348E966C97B26FE3CAD53DCCFDA28764096FFC</identifier><identifier type="ark">ark:/67375/VQC-L7000B3R-5</identifier><identifier type="DOI">10.1007/s00262-008-0556-8</identifier><identifier type="ArticleID">556</identifier><identifier type="ArticleID">s00262-008-0556-8</identifier><accessCondition type="use and reproduction" contentType="copyright">Springer-Verlag, 2008</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-3XSW68JL-F">springer</recordContentSource><recordOrigin>Springer-Verlag, 2008</recordOrigin></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/VQC-L7000B3R-5/record.json</uri></json:item></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Sante/explor/MersV1/Data/Istex/Corpus
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A22 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 000A22 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Sante
|area= MersV1
|flux= Istex
|étape= Corpus
|type= RBID
|clé= ISTEX:FB348E966C97B26FE3CAD53DCCFDA28764096FFC
|texte= Modified tumour antigen-encoding mRNA facilitates the analysis of naturally occurring and vaccine-induced CD4 and CD8 T cells in cancer patients
}}
| This area was generated with Dilib version V0.6.33. |  |