WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation
The Wilms tumor antigen, WT1, is expressed at high levels in various types of leukemia and solid tumors, including lung, breast, colon cancer and soft tissue sarcomas. The WT1 protein has been found to be highly immunogenic, and spontaneous humoral and cytotoxic T-cell responses have been detected i...
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| Veröffentlicht in: | Leukemia 2009-09, Vol.23 (9), p.1634-1642 |
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| creator | Weber, G Karbach, J Kuçi, S Kreyenberg, H Willasch, A Koscielniak, E Tonn, T Klingebiel, T Wels, W S Jäger, E Bader, P |
| description | The Wilms tumor antigen, WT1, is expressed at high levels in various types of leukemia and solid tumors, including lung, breast, colon cancer and soft tissue sarcomas. The WT1 protein has been found to be highly immunogenic, and spontaneous humoral and cytotoxic T-cell responses have been detected in patients suffering from leukemia. Furthermore, major histocompatibility complexes class I- and II-restricted WT1 peptide epitopes have been shown to elicit immune responses in patients with WT1-expressing tumors. As a consequence, WT1 has become an attractive target for anticancer immunotherapy. In this study, we investigated the feasibility of generating WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation. We analyzed the incidence of T cells specific for WT1 peptide epitopes in cancer patients and healthy volunteers. It is noted that we could generate WT1-specific responses in nine of ten healthy volunteer donors and established T-cell clones specific for two WT1-derived peptide epitopes. These
in vitro
expanded WT1-specific T cells effectively lysed WT1-expressing tumor cell lines, indicating the potential clinical impact of
ex vivo
expanded donor-derived WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation. |
| doi_str_mv | 10.1038/leu.2009.70 |
| format | Article |
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in vitro
expanded WT1-specific T cells effectively lysed WT1-expressing tumor cell lines, indicating the potential clinical impact of
ex vivo
expanded donor-derived WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation.</description><identifier>ISSN: 0887-6924</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/leu.2009.70</identifier><identifier>PMID: 19357702</identifier><identifier>CODEN: LEUKED</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Adoptive immunotherapy ; Antigens ; Biological and medical sciences ; Breast cancer ; Cancer Research ; Care and treatment ; Cell Line, Tumor ; Colon ; Colon cancer ; Critical Care Medicine ; Cytotoxicity ; Epitopes ; Ewings sarcoma ; Feasibility studies ; Graft versus host disease ; Health aspects ; Hematologic and hematopoietic diseases ; Hematology ; Hematopoietic Stem Cell Transplantation ; Histocompatibility ; HLA-A2 Antigen - analysis ; Humans ; Immunogenicity ; Immunophenotyping ; Immunotherapy ; Immunotherapy, Adoptive ; Intensive ; Internal Medicine ; Investigations ; Leukemia ; Leukemia - therapy ; Lung cancer ; Lymphocytes ; Lymphocytes T ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Oncology ; original-article ; Orthomyxoviridae - immunology ; Patients ; Peptides ; Peripheral blood ; Physiological aspects ; Sarcoma ; Sarcoma - therapy ; Skin cancer ; Soft tissues ; Solid tumors ; Stem cell transplantation ; Stem cells ; T cells ; T-Lymphocytes, Cytotoxic - immunology ; Teenagers ; Transplantation ; Transplantation, Homologous ; Tumor cell lines ; Tumors ; Volunteers ; WT1 protein ; WT1 Proteins - genetics ; WT1 Proteins - immunology</subject><ispartof>Leukemia, 2009-09, Vol.23 (9), p.1634-1642</ispartof><rights>Macmillan Publishers Limited 2009</rights><rights>2009 INIST-CNRS</rights><rights>COPYRIGHT 2009 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Sep 2009</rights><rights>Macmillan Publishers Limited 2009.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c599t-7814423049c49b4b53f0d8cbfb49e07d651afa8de8f1fd0c7efd32fbac572e483</citedby><cites>FETCH-LOGICAL-c599t-7814423049c49b4b53f0d8cbfb49e07d651afa8de8f1fd0c7efd32fbac572e483</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/leu.2009.70$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/leu.2009.70$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,2725,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21929272$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19357702$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Weber, G</creatorcontrib><creatorcontrib>Karbach, J</creatorcontrib><creatorcontrib>Kuçi, S</creatorcontrib><creatorcontrib>Kreyenberg, H</creatorcontrib><creatorcontrib>Willasch, A</creatorcontrib><creatorcontrib>Koscielniak, E</creatorcontrib><creatorcontrib>Tonn, T</creatorcontrib><creatorcontrib>Klingebiel, T</creatorcontrib><creatorcontrib>Wels, W S</creatorcontrib><creatorcontrib>Jäger, E</creatorcontrib><creatorcontrib>Bader, P</creatorcontrib><title>WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>The Wilms tumor antigen, WT1, is expressed at high levels in various types of leukemia and solid tumors, including lung, breast, colon cancer and soft tissue sarcomas. The WT1 protein has been found to be highly immunogenic, and spontaneous humoral and cytotoxic T-cell responses have been detected in patients suffering from leukemia. Furthermore, major histocompatibility complexes class I- and II-restricted WT1 peptide epitopes have been shown to elicit immune responses in patients with WT1-expressing tumors. As a consequence, WT1 has become an attractive target for anticancer immunotherapy. In this study, we investigated the feasibility of generating WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation. We analyzed the incidence of T cells specific for WT1 peptide epitopes in cancer patients and healthy volunteers. It is noted that we could generate WT1-specific responses in nine of ten healthy volunteer donors and established T-cell clones specific for two WT1-derived peptide epitopes. These
in vitro
expanded WT1-specific T cells effectively lysed WT1-expressing tumor cell lines, indicating the potential clinical impact of
ex vivo
expanded donor-derived WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation.</description><subject>Adoptive immunotherapy</subject><subject>Antigens</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Cancer Research</subject><subject>Care and treatment</subject><subject>Cell Line, Tumor</subject><subject>Colon</subject><subject>Colon cancer</subject><subject>Critical Care Medicine</subject><subject>Cytotoxicity</subject><subject>Epitopes</subject><subject>Ewings sarcoma</subject><subject>Feasibility studies</subject><subject>Graft versus host disease</subject><subject>Health aspects</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematology</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Histocompatibility</subject><subject>HLA-A2 Antigen - analysis</subject><subject>Humans</subject><subject>Immunogenicity</subject><subject>Immunophenotyping</subject><subject>Immunotherapy</subject><subject>Immunotherapy, Adoptive</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Investigations</subject><subject>Leukemia</subject><subject>Leukemia - 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genetics</subject><subject>WT1 Proteins - immunology</subject><issn>0887-6924</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqFkktv1DAUhSMEoqWwYg8WiG5gBtt5OGZXVbykSmwGsYwc-3rGlWOntoM0v4k_iTMz6lBUhLKI5Pv5HN97blE8J3hJcNm-tzAtKcZ8yfCD4pRUrFnUdU0eFqe4bdmi4bQ6KZ7EeI3xXGweFyeElzVjmJ4Wv36sCBphTEbBIo4gjTYSrZAEayNag4MgEiikgx8yF8y4yScW9dZ7hbxGGxA2bbZIeedD_IBGH6PpLSAzjNZIkYx3EWkfkFA-2_ycK8PkfJqFxi0SOkEuWutnt2weEww7f5SCcHG0wqWdzNPikRY2wrPD_6z4_unj6vLL4urb56-XF1cLWXOeFqwlVUVLXHFZ8b7q61Jj1cpe9xUHzFRTE6FFq6DVRCssGWhVUt0LWTMKVVueFed73TH4mwli6gYT5wcJB36KXcOaKo-y_i9IMS9pS2kGX_8FXvspuNxER5uqZiXNYWTq1T8pimvaEtwcpdbCQmec9nlKcvbtLrJfU7a8mVtY3kPlT8FgpHegTT6_c-H8jwv7UKO30y6-u-DbPShDTjqA7sZgBhG2HcHdvI9d3sdu3seO4Uy_OLQ09QOoI3tYwAy8OQAiSmF1TlyaeMtRwimnbObe7bmYS24N4Tib-31f7nEn0hTgVi8zM5KJ39UVAvs</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Weber, G</creator><creator>Karbach, J</creator><creator>Kuçi, S</creator><creator>Kreyenberg, H</creator><creator>Willasch, A</creator><creator>Koscielniak, E</creator><creator>Tonn, T</creator><creator>Klingebiel, T</creator><creator>Wels, W S</creator><creator>Jäger, E</creator><creator>Bader, P</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20090901</creationdate><title>WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation</title><author>Weber, G ; Karbach, J ; Kuçi, S ; Kreyenberg, H ; Willasch, A ; Koscielniak, E ; Tonn, T ; Klingebiel, T ; Wels, W S ; Jäger, E ; Bader, P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c599t-7814423049c49b4b53f0d8cbfb49e07d651afa8de8f1fd0c7efd32fbac572e483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adoptive immunotherapy</topic><topic>Antigens</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Cancer Research</topic><topic>Care and treatment</topic><topic>Cell Line, Tumor</topic><topic>Colon</topic><topic>Colon cancer</topic><topic>Critical Care Medicine</topic><topic>Cytotoxicity</topic><topic>Epitopes</topic><topic>Ewings sarcoma</topic><topic>Feasibility studies</topic><topic>Graft versus host disease</topic><topic>Health aspects</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematology</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Histocompatibility</topic><topic>HLA-A2 Antigen - analysis</topic><topic>Humans</topic><topic>Immunogenicity</topic><topic>Immunophenotyping</topic><topic>Immunotherapy</topic><topic>Immunotherapy, Adoptive</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Investigations</topic><topic>Leukemia</topic><topic>Leukemia - therapy</topic><topic>Lung cancer</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>original-article</topic><topic>Orthomyxoviridae - immunology</topic><topic>Patients</topic><topic>Peptides</topic><topic>Peripheral blood</topic><topic>Physiological aspects</topic><topic>Sarcoma</topic><topic>Sarcoma - therapy</topic><topic>Skin cancer</topic><topic>Soft tissues</topic><topic>Solid tumors</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>T cells</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>Teenagers</topic><topic>Transplantation</topic><topic>Transplantation, Homologous</topic><topic>Tumor cell lines</topic><topic>Tumors</topic><topic>Volunteers</topic><topic>WT1 protein</topic><topic>WT1 Proteins - 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Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Weber, G</au><au>Karbach, J</au><au>Kuçi, S</au><au>Kreyenberg, H</au><au>Willasch, A</au><au>Koscielniak, E</au><au>Tonn, T</au><au>Klingebiel, T</au><au>Wels, W S</au><au>Jäger, E</au><au>Bader, P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>23</volume><issue>9</issue><spage>1634</spage><epage>1642</epage><pages>1634-1642</pages><issn>0887-6924</issn><eissn>1476-5551</eissn><coden>LEUKED</coden><abstract>The Wilms tumor antigen, WT1, is expressed at high levels in various types of leukemia and solid tumors, including lung, breast, colon cancer and soft tissue sarcomas. The WT1 protein has been found to be highly immunogenic, and spontaneous humoral and cytotoxic T-cell responses have been detected in patients suffering from leukemia. Furthermore, major histocompatibility complexes class I- and II-restricted WT1 peptide epitopes have been shown to elicit immune responses in patients with WT1-expressing tumors. As a consequence, WT1 has become an attractive target for anticancer immunotherapy. In this study, we investigated the feasibility of generating WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation. We analyzed the incidence of T cells specific for WT1 peptide epitopes in cancer patients and healthy volunteers. It is noted that we could generate WT1-specific responses in nine of ten healthy volunteer donors and established T-cell clones specific for two WT1-derived peptide epitopes. These
in vitro
expanded WT1-specific T cells effectively lysed WT1-expressing tumor cell lines, indicating the potential clinical impact of
ex vivo
expanded donor-derived WT1-specific T cells for adoptive immunotherapy after allogeneic stem cell transplantation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>19357702</pmid><doi>10.1038/leu.2009.70</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Leukemia, 2009-09, Vol.23 (9), p.1634-1642 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Nature Journals Online; SpringerLink Journals - AutoHoldings |
| subjects | Adoptive immunotherapy Antigens Biological and medical sciences Breast cancer Cancer Research Care and treatment Cell Line, Tumor Colon Colon cancer Critical Care Medicine Cytotoxicity Epitopes Ewings sarcoma Feasibility studies Graft versus host disease Health aspects Hematologic and hematopoietic diseases Hematology Hematopoietic Stem Cell Transplantation Histocompatibility HLA-A2 Antigen - analysis Humans Immunogenicity Immunophenotyping Immunotherapy Immunotherapy, Adoptive Intensive Internal Medicine Investigations Leukemia Leukemia - therapy Lung cancer Lymphocytes Lymphocytes T Medical prognosis Medical sciences Medicine Medicine & Public Health Oncology original-article Orthomyxoviridae - immunology Patients Peptides Peripheral blood Physiological aspects Sarcoma Sarcoma - therapy Skin cancer Soft tissues Solid tumors Stem cell transplantation Stem cells T cells T-Lymphocytes, Cytotoxic - immunology Teenagers Transplantation Transplantation, Homologous Tumor cell lines Tumors Volunteers WT1 protein WT1 Proteins - genetics WT1 Proteins - immunology |
| title | WT1 peptide-specific T cells generated from peripheral blood of healthy donors: possible implications for adoptive immunotherapy after allogeneic stem cell transplantation |
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