Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine
Identifieur interne : 002720 ( Istex/Corpus ); précédent : 002719; suivant : 002721Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine
Auteurs : Kwong Y. Tsang ; Sam Zaremba ; Carol A. Nieroda ; Ming Z. Zhu ; J. Michael Hamilton ; Jeffrey SchlomSource :
- JNCI: Journal of the National Cancer Institute [ 0027-8874 ] ; 1995.
Abstract
Background: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. Purpose: Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. Methods: Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. Results: While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. Conclusions: This study demonstrates for the First time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. Implications: These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]
Url:
DOI: 10.1093/jnci/87.13.982
Links to Exploration step
ISTEX:1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77Le document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title><author><name sortKey="Tsang, Kwong Y" sort="Tsang, Kwong Y" uniqKey="Tsang K" first="Kwong Y." last="Tsang">Kwong Y. Tsang</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Zaremba, Sam" sort="Zaremba, Sam" uniqKey="Zaremba S" first="Sam" last="Zaremba">Sam Zaremba</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Nieroda, Carol A" sort="Nieroda, Carol A" uniqKey="Nieroda C" first="Carol A." last="Nieroda">Carol A. Nieroda</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Zhu, Ming Z" sort="Zhu, Ming Z" uniqKey="Zhu M" first="Ming Z." last="Zhu">Ming Z. Zhu</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Hamilton, J Michael" sort="Hamilton, J Michael" uniqKey="Hamilton J" first="J. Michael" last="Hamilton">J. Michael Hamilton</name><affiliation><mods:affiliation>NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Schlom, Jeffrey" sort="Schlom, Jeffrey" uniqKey="Schlom J" first="Jeffrey" last="Schlom">Jeffrey Schlom</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</mods:affiliation></affiliation><affiliation><mods:affiliation>*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</mods:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77</idno><date when="1995" year="1995">1995</date><idno type="doi">10.1093/jnci/87.13.982</idno><idno type="url">https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/fulltext.pdf</idno><idno type="wicri:Area/Istex/Corpus">002720</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">002720</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main">Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title><author><name sortKey="Tsang, Kwong Y" sort="Tsang, Kwong Y" uniqKey="Tsang K" first="Kwong Y." last="Tsang">Kwong Y. Tsang</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Zaremba, Sam" sort="Zaremba, Sam" uniqKey="Zaremba S" first="Sam" last="Zaremba">Sam Zaremba</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Nieroda, Carol A" sort="Nieroda, Carol A" uniqKey="Nieroda C" first="Carol A." last="Nieroda">Carol A. Nieroda</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Zhu, Ming Z" sort="Zhu, Ming Z" uniqKey="Zhu M" first="Ming Z." last="Zhu">Ming Z. Zhu</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Hamilton, J Michael" sort="Hamilton, J Michael" uniqKey="Hamilton J" first="J. Michael" last="Hamilton">J. Michael Hamilton</name><affiliation><mods:affiliation>NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation></author><author><name sortKey="Schlom, Jeffrey" sort="Schlom, Jeffrey" uniqKey="Schlom J" first="Jeffrey" last="Schlom">Jeffrey Schlom</name><affiliation><mods:affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</mods:affiliation></affiliation><affiliation><mods:affiliation>Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</mods:affiliation></affiliation><affiliation><mods:affiliation>*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">JNCI: Journal of the National Cancer Institute</title><idno type="eISSN">1460-2105</idno><idno type="ISSN">0027-8874</idno><imprint><publisher>Oxford University Press</publisher><date type="published">1995</date><biblScope unit="vol">87</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="982">982</biblScope><biblScope unit="page" to="990">990</biblScope></imprint><idno type="ISSN">0027-8874</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0027-8874</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. Purpose: Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. Methods: Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. Results: While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. Conclusions: This study demonstrates for the First time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. Implications: These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]</div></front></TEI><istex><corpusName>oup</corpusName><keywords><teeft><json:string>peptide</json:string><json:string>lysis</json:string><json:string>vaccinia</json:string><json:string>pbls</json:string><json:string>carcinoembryonic</json:string><json:string>cytotoxic</json:string><json:string>epitope</json:string><json:string>recombinant</json:string><json:string>lymphocyte</json:string><json:string>autologous</json:string><json:string>carcinoma</json:string><json:string>national cancer institute</json:string><json:string>colorectal</json:string><json:string>cell line</json:string><json:string>vaccinia virus</json:string><json:string>carcinoembryonic antigen</json:string><json:string>immunol</json:string><json:string>complete medium</json:string><json:string>july</json:string><json:string>immune</json:string><json:string>metastatic</json:string><json:string>becton</json:string><json:string>cytotoxicity</json:string><json:string>cytometry</json:string><json:string>assay</json:string><json:string>vaccine</json:string><json:string>life technology</json:string><json:string>flow cytometry</json:string><json:string>becton dickinson</json:string><json:string>amino</json:string><json:string>human cytotoxic</json:string><json:string>release assay</json:string><json:string>specific epitope</json:string><json:string>preimmunization pbls</json:string><json:string>immune complex</json:string><json:string>retroviral vector</json:string><json:string>target cell</json:string><json:string>consensus motif</json:string><json:string>significant lysis</json:string><json:string>anchor residue</json:string><json:string>immunization</json:string><json:string>dickinson</json:string><json:string>previous study</json:string><json:string>flow cytometric analysis</json:string><json:string>recombinant vaccinia virus</json:string><json:string>peptide sequence</json:string><json:string>potential target</json:string><json:string>bovine serum albumin</json:string><json:string>natl cancer inst</json:string><json:string>spontaneous release</json:string><json:string>tumor cell</json:string><json:string>nonhuman primate</json:string><json:string>surgery branch</json:string><json:string>prostate specific antigen</json:string><json:string>cytotoxic response</json:string><json:string>metastatic carcinoma</json:string><json:string>cell growth</json:string><json:string>optimal alignment</json:string><json:string>amino acid</json:string><json:string>colorectal cancer</json:string><json:string>colon</json:string><json:string>vaccination</json:string><json:string>molecule</json:string><json:string>peptide binding</json:string><json:string>positive control</json:string><json:string>patient vac7</json:string><json:string>patient vac6</json:string><json:string>primary lymphoproliferative response</json:string><json:string>assay plate</json:string><json:string>costar corp</json:string><json:string>final concentration</json:string><json:string>clinical trial</json:string><json:string>same peptide</json:string><json:string>immune response</json:string><json:string>effector cell</json:string><json:string>human apc</json:string><json:string>animal model study</json:string><json:string>national institute</json:string><json:string>human response</json:string><json:string>fetal tissue</json:string><json:string>lung cancer</json:string><json:string>binding peptide</json:string><json:string>teknika corp</json:string><json:string>west chester</json:string><json:string>endogenously process</json:string><json:string>blue laser</json:string><json:string>fluorescein conjugate</json:string><json:string>phycoerythrin conjugate</json:string><json:string>freeze clinical system</json:string><json:string>patient vacol</json:string><json:string>vaccinia virus vector</json:string><json:string>amino acid sequence</json:string><json:string>predictive algorithm</json:string><json:string>colon carcinoma cell line</json:string><json:string>human colon carcinoma cell line</json:string><json:string>cell culture</json:string><json:string>therion biology corporation</json:string><json:string>peripheral blood lymphocyte</json:string><json:string>lyse autologous</json:string><json:string>positive well</json:string><json:string>peripheral blood mononuclear cell</json:string><json:string>article journal</json:string><json:string>recombinant vaccine</json:string><json:string>entire human</json:string><json:string>cell surface</json:string><json:string>human carcinoma cell</json:string><json:string>carcinoma cell</json:string><json:string>percent specific lysis</json:string><json:string>gastrointestinal cancer patient</json:string><json:string>experimental model</json:string><json:string>human carcinoembryonic antigen</json:string><json:string>recombinant vaccinia virus vaccine</json:string><json:string>jeffrey schlom</json:string><json:string>proc natl acad</json:string><json:string>metastatic melanoma</json:string><json:string>antigen</json:string></teeft></keywords><author><json:item><name>Kwong Y. Tsang</name><affiliations><json:string>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</json:string></affiliations></json:item><json:item><name>Sam Zaremba</name><affiliations><json:string>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</json:string></affiliations></json:item><json:item><name>Carol A. Nieroda</name><affiliations><json:string>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</json:string></affiliations></json:item><json:item><name>Ming Z. Zhu</name><affiliations><json:string>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</json:string></affiliations></json:item><json:item><name>J. Michael Hamilton</name><affiliations><json:string>NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute Bethesda, Md.</json:string></affiliations></json:item><json:item><name>Jeffrey Schlom</name><affiliations><json:string>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</json:string><json:string>Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</json:string><json:string>*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</json:string></affiliations></json:item></author><articleId><json:string>87.13.982</json:string></articleId><arkIstex>ark:/67375/HXZ-0NQWQKHW-W</arkIstex><language><json:string>unknown</json:string></language><originalGenre><json:string>research-article</json:string></originalGenre><abstract>Background: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. Purpose: Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. Methods: Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. Results: While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. Conclusions: This study demonstrates for the First time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. Implications: These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]</abstract><qualityIndicators><score>8</score><pdfWordCount>7467</pdfWordCount><pdfCharCount>45705</pdfCharCount><pdfVersion>1.2</pdfVersion><pdfPageCount>9</pdfPageCount><pdfPageSize>606 x 797 pts</pdfPageSize><pdfWordsPerPage>830</pdfWordsPerPage><pdfText>true</pdfText><refBibsNative>false</refBibsNative><abstractWordCount>380</abstractWordCount><abstractCharCount>2553</abstractCharCount><keywordCount>0</keywordCount></qualityIndicators><title>Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title><pmid><json:string>7629885</json:string></pmid><genre><json:string>research-article</json:string></genre><host><title>JNCI: Journal of the National Cancer Institute</title><language><json:string>unknown</json:string></language><issn><json:string>0027-8874</json:string></issn><eissn><json:string>1460-2105</json:string></eissn><publisherId><json:string>jnci</json:string></publisherId><volume>87</volume><issue>13</issue><pages><first>982</first><last>990</last></pages><genre><json:string>journal</json:string></genre><subject><json:item><value>ARTICLES</value></json:item></subject></host><namedEntities><unitex><date><json:string>1995</json:string></date><geogName></geogName><orgName><json:string>National Cancer Instituie, Bethesda, Md</json:string><json:string>Division of Cancer Treatment</json:string><json:string>Division of Cancer Biology</json:string><json:string>National Institutes of Health</json:string></orgName><orgName_funder></orgName_funder><orgName_provider></orgName_provider><persName><json:string>Ming Z. Zhu</json:string><json:string>S. Zaremba</json:string><json:string>Jeffrey Schlom</json:string><json:string>Y. Tsang</json:string><json:string>Sam Zaremba</json:string><json:string>Michael Hamilton</json:string><json:string>J. M. Hamilton</json:string><json:string>M. Z. Zhu</json:string><json:string>J. Schlom</json:string><json:string>K. Y. Tsang</json:string><json:string>C. A. Nieroda</json:string><json:string>Carol A. Nieroda</json:string></persName><placeName></placeName><ref_url></ref_url><ref_bibl></ref_bibl><bibl></bibl></unitex></namedEntities><ark><json:string>ark:/67375/HXZ-0NQWQKHW-W</json:string></ark><categories><wos><json:string>1 - science</json:string><json:string>2 - oncology</json:string></wos><scienceMetrix><json:string>1 - health sciences</json:string><json:string>2 - clinical medicine</json:string><json:string>3 - oncology & carcinogenesis</json:string></scienceMetrix><scopus><json:string>1 - Life Sciences</json:string><json:string>2 - Biochemistry, Genetics and Molecular Biology</json:string><json:string>3 - Cancer Research</json:string><json:string>1 - Health Sciences</json:string><json:string>2 - Medicine</json:string><json:string>3 - Oncology</json:string></scopus><inist><json:string>1 - sciences appliquees, technologies et medecines</json:string><json:string>2 - sciences biologiques et medicales</json:string><json:string>3 - sciences medicales</json:string></inist></categories><publicationDate>1995</publicationDate><copyrightDate>1995</copyrightDate><doi><json:string>10.1093/jnci/87.13.982</json:string></doi><id>1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/fulltext.pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/bundle.zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/fulltext.tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main">Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Oxford University Press</publisher><availability><licence>© Oxford University Press</licence></availability><date type="Copyright" when="1995">1995</date><date type="published">1995</date></publicationStmt><notesStmt><note type="content-type" source="research-article" scheme="https://content-type.data.istex.fr/ark:/67375/XTP-1JC4F85T-7">research-article</note><note type="publication-type" scheme="https://publication-type.data.istex.fr/ark:/67375/JMC-0GLKJH51-B">journal</note></notesStmt><sourceDesc><biblStruct type="article"><analytic><title level="a" type="main">Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title><author xml:id="author-0000"><persName><surname>Tsang</surname><forename type="first">Kwong Y.</forename></persName><affiliation><orgName type="institution">Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation></author><author xml:id="author-0001"><persName><surname>Zaremba</surname><forename type="first">Sam</forename></persName><affiliation><orgName type="institution">Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation></author><author xml:id="author-0002"><persName><surname>Nieroda</surname><forename type="first">Carol A.</forename></persName><affiliation><orgName type="institution">Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation></author><author xml:id="author-0003"><persName><surname>Zhu</surname><forename type="first">Ming Z.</forename></persName><affiliation><orgName type="institution">Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation></author><author xml:id="author-0004"><persName><surname>Hamilton</surname><forename type="first">J. Michael</forename></persName><affiliation><orgName type="institution">NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation></author><author xml:id="author-0005"><persName><surname>Schlom</surname><forename type="first">Jeffrey</forename></persName><affiliation><orgName type="institution">Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</orgName><address><addrLine>Bethesda, Md.</addrLine></address></affiliation><affiliation role="corresp">*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</affiliation></author><idno type="istex">1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77</idno><idno type="ark">ark:/67375/HXZ-0NQWQKHW-W</idno><idno type="publisher-id">87.13.982</idno><idno type="DOI">10.1093/jnci/87.13.982</idno></analytic><monogr><title level="j" type="main">JNCI: Journal of the National Cancer Institute</title><idno type="hwp">jnci</idno><idno type="publisher-id">jnci</idno><idno type="pmc">jnci</idno><idno type="eISSN">1460-2105</idno><idno type="pISSN">0027-8874</idno><imprint><publisher>Oxford University Press</publisher><date type="published">1995</date><biblScope unit="vol">87</biblScope><biblScope unit="issue">13</biblScope><biblScope unit="page" from="982">982</biblScope><biblScope unit="page" to="990">990</biblScope></imprint></monogr></biblStruct></sourceDesc></fileDesc><encodingDesc><schemaRef type="ODD" url="https://xml-schema.delivery.istex.fr/tei-istex.odd"></schemaRef><appInfo><application ident="pub2tei" version="1.0.41" when="2020-04-06"><label>pub2TEI-ISTEX</label><desc>A set of style sheets for converting XML documents encoded in various scientific publisher formats into a common TEI format.
<ref target="http://www.tei-c.org/">We use TEI</ref></desc></application></appInfo></encodingDesc><profileDesc><abstract><p><hi rend="italic">Background:</hi> The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. <hi rend="italic">Purpose:</hi> Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. <hi rend="italic">Methods:</hi> Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. <hi rend="italic">Results:</hi> While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8<hi rend="superscript">+</hi>/CD4<hi rend="superscript">+</hi> double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. <hi rend="italic">Conclusions:</hi> This study demonstrates for the First time (<hi rend="italic">a</hi>) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (<hi rend="italic">b</hi>) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (<hi rend="italic">c</hi>) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. <hi rend="italic">Implications:</hi> These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]</p></abstract><textClass ana="subject"><keywords scheme="subject"><term>ARTICLES</term></keywords></textClass><langUsage><language ident="EN"></language></langUsage></profileDesc><revisionDesc><change when="2020-04-06" who="#istex" xml:id="pub2tei">formatting</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/fulltext.txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="corpus oup, element #text not found" wicri:toSee="no header"><istex:docType PUBLIC="-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" URI="journalpublishing.dtd" name="istex:docType"></istex:docType><istex:document><article article-type="research-article">
<front>
<journal-meta>
<journal-id journal-id-type="hwp">jnci</journal-id>
<journal-id journal-id-type="publisher-id">jnci</journal-id>
<journal-id journal-id-type="pmc">jnci</journal-id>
<journal-title>JNCI: Journal of the National Cancer Institute</journal-title>
<issn pub-type="epub">1460-2105</issn>
<issn pub-type="ppub">0027-8874</issn>
<publisher>
<publisher-name>Oxford University Press</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">87.13.982</article-id>
<article-id pub-id-type="doi">10.1093/jnci/87.13.982</article-id>
<article-categories>
<subj-group>
<subject>ARTICLES</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Tsang</surname><given-names>Kwong Y.</given-names></name><xref ref-type="aff" rid="au1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zaremba</surname><given-names>Sam</given-names></name><xref ref-type="aff" rid="au1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Nieroda</surname><given-names>Carol A.</given-names></name><xref ref-type="aff" rid="au1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhu</surname><given-names>Ming Z.</given-names></name><xref ref-type="aff" rid="au1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Hamilton</surname><given-names>J. Michael</given-names></name><xref ref-type="aff" rid="au2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Schlom</surname><given-names>Jeffrey</given-names></name><xref ref-type="aff" rid="au1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref>
</contrib>
<aff id="au1"><sup>1</sup><institution>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute</institution> <addr-line>Bethesda, Md.</addr-line></aff>
<aff id="au2"><sup>2</sup><institution>NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute</institution> <addr-line>Bethesda, Md.</addr-line></aff>
</contrib-group>
<author-notes>
<corresp id="cor1"><sup>*</sup>Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>05</day>
<month>7</month>
<year>1995</year>
</pub-date>
<volume>87</volume>
<issue>13</issue>
<fpage>982</fpage>
<lpage>990</lpage>
<copyright-statement>© Oxford University Press</copyright-statement>
<copyright-year>1995</copyright-year>
<abstract>
<p><italic>Background:</italic> The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. <italic>Purpose:</italic> Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. <italic>Methods:</italic> Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. <italic>Results:</italic> While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8<sup>+</sup>/CD4<sup>+</sup> double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. <italic>Conclusions:</italic> This study demonstrates for the First time (<italic>a</italic>) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (<italic>b</italic>) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (<italic>c</italic>) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. <italic>Implications:</italic> These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]</p>
</abstract>
</article-meta>
</front>
</article></istex:document></istex:metadataXml><mods version="3.6"><titleInfo><title>Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title></titleInfo><titleInfo type="alternative" contentType="CDATA"><title>Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine</title></titleInfo><name type="personal"><namePart type="given">Kwong Y.</namePart><namePart type="family">Tsang</namePart><affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Sam</namePart><namePart type="family">Zaremba</namePart><affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Carol A.</namePart><namePart type="family">Nieroda</namePart><affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ming Z.</namePart><namePart type="family">Zhu</namePart><affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">J. Michael</namePart><namePart type="family">Hamilton</namePart><affiliation>NCI-Navy Medical Oncology Branch, Division of Cancer Treatment, National Cancer Institute Bethesda, Md.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Jeffrey</namePart><namePart type="family">Schlom</namePart><affiliation>Laboratory of Tumor Immunology and Biology, Division of Cancer Biology, Diagnosis, and Centers, National Cancer Institute Bethesda, Md.</affiliation><affiliation>Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</affiliation><affiliation>*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</affiliation><role><roleTerm type="text">author</roleTerm></role></name><typeOfResource>text</typeOfResource><genre type="research-article" displayLabel="research-article" 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>Oxford University Press</publisher><dateIssued encoding="w3cdtf">1995-07-05</dateIssued><copyrightDate encoding="w3cdtf">1995</copyrightDate></originInfo><abstract>Background: The human carcinoembryonic antigen (CEA), which is expressed in several cancer types, is a potential target for specific immunotherapy using recombinant vaccines. Previous studies have shown that when the CEA gene is placed into vaccinia virus, the recombinant vaccine (rV-CEA) can elicit T-cell responses in both rodents and non-human primates. Purpose: Our objective was to determine if rV-CEA could elicit CEA-specific T-cell responses in humans with appropriate human leukocyte antigen (HLA) motifs. Methods: Peripheral blood lymphocytes (PBLs) obtained from patients with metastatic carcinoma, both before and after vaccination with rV-CEA, were analyzed for T-cell response to specific 9- to 11-mer CEA peptides selected to conform to human HLA class I-A2 motifs. Results: While little or no T-cell growth was seen from preimmunization PBLs of patients pulsed with CEA peptides and interleukin 2 (IL-2), T-cell lines were obtained from PBLs of patients after vaccination with one to three cycles of stimulation. Cytolytic T-cell lines from three HLA-A2 patients were established with a 9-amino acid peptide (CAP-1), and the CD8+/CD4+ double-positive T-cell line (V24T) was chosen for detailed analysis. When autologous Epstein-Barr virus (EBV)-transformed B cells were either incubated with CAP-1 peptide or transduced with the CEA gene using a retroviral vector, they were lysed by the V24T cell line, but allogeneic non-A2 EBV-transformed B cells were not. The SW403 human colon carcinoma cell line, which is CEA positive and HLA-A2 positive, was also lysed by the V24T cell line, while two non-HLA-A2 CEA-positive colon carcinoma cell lines were not. To further confirm the class I HLA-A2 restricted nature of the V24T cytotoxicity, the non-HLA-A2 SW837 CEA-expressing colon carcinoma cell line was infected with a recombinant vaccinia virus expressing the HLA class I-A2 gene, and it became susceptible to V24T lysis. Cells infected with vector alone were not lysed. Conclusions: This study demonstrates for the First time (a) the ability to generate a human cytolytic T-cell response to specific epitopes of CEA, (b) the class I HLA-A2 restricted nature of the T-cell mediated lysis, and (c) the ability of human tumor cells to endogenously process CEA to present a specific CEA peptide in the context of major histocompatibility complex for T-cell-mediated lysis. Implications: These findings have implications in the development of specific second-generation cancer immunotherapy protocols. [J Natl Cancer Inst 87:982–;990,1995]</abstract><note type="author-notes">*Correspondence to: Jeffrey Schlom, Ph.D., National Institutes of Health, Bldg, 10, Rm. 8B07, Bethesda, MD 20892.</note><relatedItem type="host"><titleInfo><title>JNCI: Journal of the National Cancer Institute</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><subject><topic>ARTICLES</topic></subject><identifier type="ISSN">0027-8874</identifier><identifier type="eISSN">1460-2105</identifier><identifier type="PublisherID">jnci</identifier><identifier type="PublisherID-hwp">jnci</identifier><part><date>1995</date><detail type="volume"><caption>vol.</caption><number>87</number></detail><detail type="issue"><caption>no.</caption><number>13</number></detail><extent unit="pages"><start>982</start><end>990</end></extent></part></relatedItem><identifier type="istex">1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77</identifier><identifier type="ark">ark:/67375/HXZ-0NQWQKHW-W</identifier><identifier type="DOI">10.1093/jnci/87.13.982</identifier><identifier type="ArticleID">87.13.982</identifier><accessCondition type="use and reproduction" contentType="copyright">© Oxford University Press</accessCondition><recordInfo><recordContentSource authority="ISTEX" authorityURI="https://loaded-corpus.data.istex.fr" valueURI="https://loaded-corpus.data.istex.fr/ark:/67375/XBH-GTWS0RDP-M">oup</recordContentSource><recordOrigin>Converted from (version 1.2.10) to MODS version 3.6.</recordOrigin><recordCreationDate encoding="w3cdtf">2020-04-17</recordCreationDate></recordInfo></mods><json:item><extension>json</extension><original>false</original><mimetype>application/json</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/record.json</uri></json:item></metadata><annexes><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/ark:/67375/HXZ-0NQWQKHW-W/annexes.pdf</uri></json:item></annexes><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 002720 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Corpus/biblio.hfd -nk 002720 | 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:1A9CA5D0C3A08D42175E9D97112A7CB2248D4B77
|texte= Generation of Human Cytotoxic T Cells Specific for Human Carcinoembryonic Antigen Epitopes From Patients Immunized With Recombinant Vaccinia-CEA Vaccine
}}
| This area was generated with Dilib version V0.6.33. |  |