T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine
The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or...
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| Veröffentlicht in: | Vaccine 2005-03, Vol.23 (19), p.2439-2453 |
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| creator | Haas, Claudia Lulei, Maria Fournier, Philippe Arnold, Annette Schirrmacher, Volker |
| description | The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety. |
| doi_str_mv | 10.1016/j.vaccine.2004.10.031 |
| format | Article |
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We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2004.10.031</identifier><identifier>PMID: 15752830</identifier><identifier>CODEN: VACCDE</identifier><language>eng</language><publisher>Oxford: Elsevier Ltd</publisher><subject>Animals ; Antibodies - genetics ; Antibodies - immunology ; Antigens ; Antigens, CD - analysis ; Antigens, Differentiation, T-Lymphocyte - analysis ; Antigens, Viral - genetics ; Antigens, Viral - immunology ; Applied microbiology ; Biological and medical sciences ; Bispecific single chain antibody ; Cancer Vaccines - genetics ; Cancer Vaccines - immunology ; CD28 Antigens - immunology ; CD3 and CD28 cross-linking ; CD3 Complex - immunology ; Cell Line, Tumor ; Cytokines ; Cytokines - analysis ; Cytotoxicity ; Cytotoxicity, Immunologic ; Fundamental and applied biological sciences. Psychology ; HN Protein - immunology ; Humans ; Immune system ; Immunoglobulin Variable Region - genetics ; Immunoglobulin Variable Region - immunology ; Lectins, C-Type ; Lymphocyte Activation ; Lymphokines - analysis ; Medical sciences ; Mice ; Microbiology ; Miscellaneous ; Newcastle disease ; Newcastle Disease Virus ; Newcastle disease virus - immunology ; Receptors, Interleukin-2 - analysis ; Rodents ; T cell receptors ; T-Lymphocytes - immunology ; Tumors ; Vaccines ; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) ; Virology</subject><ispartof>Vaccine, 2005-03, Vol.23 (19), p.2439-2453</ispartof><rights>2004 Elsevier Ltd</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Elsevier Limited Mar 31, 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-1f53c299cba633be53bcab99d823bc5b46a3344cefcb84864baea585d17630bc3</citedby><cites>FETCH-LOGICAL-c485t-1f53c299cba633be53bcab99d823bc5b46a3344cefcb84864baea585d17630bc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1559074155?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17589154$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15752830$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Haas, Claudia</creatorcontrib><creatorcontrib>Lulei, Maria</creatorcontrib><creatorcontrib>Fournier, Philippe</creatorcontrib><creatorcontrib>Arnold, Annette</creatorcontrib><creatorcontrib>Schirrmacher, Volker</creatorcontrib><title>T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.</description><subject>Animals</subject><subject>Antibodies - genetics</subject><subject>Antibodies - immunology</subject><subject>Antigens</subject><subject>Antigens, CD - analysis</subject><subject>Antigens, Differentiation, T-Lymphocyte - analysis</subject><subject>Antigens, Viral - genetics</subject><subject>Antigens, Viral - immunology</subject><subject>Applied microbiology</subject><subject>Biological and medical sciences</subject><subject>Bispecific single chain antibody</subject><subject>Cancer Vaccines - genetics</subject><subject>Cancer Vaccines - immunology</subject><subject>CD28 Antigens - immunology</subject><subject>CD3 and CD28 cross-linking</subject><subject>CD3 Complex - immunology</subject><subject>Cell Line, Tumor</subject><subject>Cytokines</subject><subject>Cytokines - analysis</subject><subject>Cytotoxicity</subject><subject>Cytotoxicity, Immunologic</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HN Protein - immunology</subject><subject>Humans</subject><subject>Immune system</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulin Variable Region - immunology</subject><subject>Lectins, C-Type</subject><subject>Lymphocyte Activation</subject><subject>Lymphokines - analysis</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Newcastle disease</subject><subject>Newcastle Disease Virus</subject><subject>Newcastle disease virus - immunology</subject><subject>Receptors, Interleukin-2 - analysis</subject><subject>Rodents</subject><subject>T cell receptors</subject><subject>T-Lymphocytes - immunology</subject><subject>Tumors</subject><subject>Vaccines</subject><subject>Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects)</subject><subject>Virology</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkU1r3DAQhkVpabZpf0KLoLQ3bSRLsuVTCduPBAK5pNCb0Md4o60tp5K9kH9fuWsI9JLTDDPPDO_Mi9B7RreMsvrisD0a50KEbUWpKLUt5ewF2jDVcFJJpl6iDa1qQQSjv87Qm5wPlFLJWfsanTHZyEpxukH3d8RB3-Mphf0eUoh7bB_x7isn2ERfkkoRG6JfGsPYg5t7yLgP8Td4PI3Y4Pt5MBEfQ5ozGUYfurB05mFM-N_mVeZb9KozfYZ3azxHP79_u9tdkZvbH9e7yxvihJITYZ3krmpbZ03NuQXJrTO2bb2qSiatqA3nQjjonFVC1cIaMFJJz5qaU-v4Ofp82vuQxj8z5EkPIS9CTIRxzrpuJKWsZc-CrFFFQd0W8ON_4GGcUyxHaCZlSxtRQqHkiXJpzDlBpx9SGEx61IzqxTF90Osr9OLYUi6OlbkP6_bZDuCfplaLCvBpBUx2pu-SiS7kJ66RqmVSFO7LiYPy3WOApLMLEB34kMBN2o_hGSl_AePFtWs</recordid><startdate>20050331</startdate><enddate>20050331</enddate><creator>Haas, Claudia</creator><creator>Lulei, Maria</creator><creator>Fournier, Philippe</creator><creator>Arnold, Annette</creator><creator>Schirrmacher, Volker</creator><general>Elsevier Ltd</general><general>Elsevier</general><general>Elsevier Limited</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>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050331</creationdate><title>T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine</title><author>Haas, Claudia ; Lulei, Maria ; Fournier, Philippe ; Arnold, Annette ; Schirrmacher, Volker</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-1f53c299cba633be53bcab99d823bc5b46a3344cefcb84864baea585d17630bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Animals</topic><topic>Antibodies - genetics</topic><topic>Antibodies - immunology</topic><topic>Antigens</topic><topic>Antigens, CD - analysis</topic><topic>Antigens, Differentiation, T-Lymphocyte - analysis</topic><topic>Antigens, Viral - genetics</topic><topic>Antigens, Viral - immunology</topic><topic>Applied microbiology</topic><topic>Biological and medical sciences</topic><topic>Bispecific single chain antibody</topic><topic>Cancer Vaccines - genetics</topic><topic>Cancer Vaccines - immunology</topic><topic>CD28 Antigens - immunology</topic><topic>CD3 and CD28 cross-linking</topic><topic>CD3 Complex - immunology</topic><topic>Cell Line, Tumor</topic><topic>Cytokines</topic><topic>Cytokines - analysis</topic><topic>Cytotoxicity</topic><topic>Cytotoxicity, Immunologic</topic><topic>Fundamental and applied biological sciences. 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Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Haas, Claudia</au><au>Lulei, Maria</au><au>Fournier, Philippe</au><au>Arnold, Annette</au><au>Schirrmacher, Volker</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2005-03-31</date><risdate>2005</risdate><volume>23</volume><issue>19</issue><spage>2439</spage><epage>2453</epage><pages>2439-2453</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><coden>VACCDE</coden><abstract>The aim was to develop T cell costimulatory molecules that are broadly applicable to augment anti-tumor immune responses upon application of a virus-modified tumor vaccine to cancer patients. We generated recombinant bispecific single-chain antibodies with one specificity directed against the CD3 or the CD28 antigen on human T cells and the other against the viral target molecule hemagglutinin-neuraminidase (HN) of Newcastle Disease Virus (NDV). By re-directing unstimulated primary human T cells against HN-expressing NDV-infected tumor cells, the bispecific molecule bsHN-CD3 cross-linked effector and target cells and rapidly induced cytotoxicity at nanomolar concentrations. The bsHN-CD28 molecule exerted T cell co-stimulatory function. Maximal T cell activation was achieved with tumor cells infected by NDV and modified with both new stimulatory molecules. This was revealed by T cell proliferation, upregulation of CD69 and CD25 and by release of cytokines, interferons and chemokines. The new molecules combine high-effectivity with specificity and safety.</abstract><cop>Oxford</cop><pub>Elsevier Ltd</pub><pmid>15752830</pmid><doi>10.1016/j.vaccine.2004.10.031</doi><tpages>15</tpages></addata></record> |
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| ispartof | Vaccine, 2005-03, Vol.23 (19), p.2439-2453 |
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| subjects | Animals Antibodies - genetics Antibodies - immunology Antigens Antigens, CD - analysis Antigens, Differentiation, T-Lymphocyte - analysis Antigens, Viral - genetics Antigens, Viral - immunology Applied microbiology Biological and medical sciences Bispecific single chain antibody Cancer Vaccines - genetics Cancer Vaccines - immunology CD28 Antigens - immunology CD3 and CD28 cross-linking CD3 Complex - immunology Cell Line, Tumor Cytokines Cytokines - analysis Cytotoxicity Cytotoxicity, Immunologic Fundamental and applied biological sciences. Psychology HN Protein - immunology Humans Immune system Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - immunology Lectins, C-Type Lymphocyte Activation Lymphokines - analysis Medical sciences Mice Microbiology Miscellaneous Newcastle disease Newcastle Disease Virus Newcastle disease virus - immunology Receptors, Interleukin-2 - analysis Rodents T cell receptors T-Lymphocytes - immunology Tumors Vaccines Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects) Virology |
| title | T-cell triggering by CD3- and CD28-binding molecules linked to a human virus-modified tumor cell vaccine |
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