DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells
Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted v...
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Veröffentlicht in: | Molecular therapy 2006-04, Vol.13 (4), p.776-785 |
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description | Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC. |
doi_str_mv | 10.1016/j.ymthe.2005.10.019 |
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We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1016/j.ymthe.2005.10.019</identifier><identifier>PMID: 16414309</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Animals ; Antibodies ; Antigen-Presenting Cells - immunology ; Antigens ; Antigens, Neoplasm - genetics ; Antigens, Neoplasm - immunology ; Chemokines ; Dimerization ; Electroporation ; Gene therapy ; Histocompatibility Antigens Class II - immunology ; Immunoglobulin Idiotypes - genetics ; Immunoglobulin Idiotypes - immunology ; Injections, Intramuscular ; Lymphocytes ; Lymphoma ; Lymphoma, B-Cell - immunology ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Mice, Transgenic ; Models, Immunological ; Multiple myeloma ; Multiple Myeloma - immunology ; Neoplasms, Experimental - immunology ; Neoplasms, Experimental - prevention & control ; Plasmids ; Proteins ; Recombinant Fusion Proteins - immunology ; Time Factors ; Tumors ; Vaccination ; Vaccines ; Vaccines, DNA - chemistry ; Vaccines, DNA - immunology</subject><ispartof>Molecular therapy, 2006-04, Vol.13 (4), p.776-785</ispartof><rights>Copyright Nature Publishing Group Apr 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c496t-48b4eeed682f85c71e9c0f752578e43fcd6f225f1db798c0fe9d4b6788c4b0cf3</citedby><cites>FETCH-LOGICAL-c496t-48b4eeed682f85c71e9c0f752578e43fcd6f225f1db798c0fe9d4b6788c4b0cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/1792806380?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16414309$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fredriksen, Agnete B</creatorcontrib><creatorcontrib>Sandlie, Inger</creatorcontrib><creatorcontrib>Bogen, Bjarne</creatorcontrib><title>DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC.</description><subject>Animals</subject><subject>Antibodies</subject><subject>Antigen-Presenting Cells - immunology</subject><subject>Antigens</subject><subject>Antigens, Neoplasm - genetics</subject><subject>Antigens, Neoplasm - immunology</subject><subject>Chemokines</subject><subject>Dimerization</subject><subject>Electroporation</subject><subject>Gene therapy</subject><subject>Histocompatibility Antigens Class II - immunology</subject><subject>Immunoglobulin Idiotypes - genetics</subject><subject>Immunoglobulin Idiotypes - immunology</subject><subject>Injections, Intramuscular</subject><subject>Lymphocytes</subject><subject>Lymphoma</subject><subject>Lymphoma, B-Cell - immunology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, SCID</subject><subject>Mice, Transgenic</subject><subject>Models, Immunological</subject><subject>Multiple myeloma</subject><subject>Multiple Myeloma - immunology</subject><subject>Neoplasms, Experimental - immunology</subject><subject>Neoplasms, Experimental - prevention & control</subject><subject>Plasmids</subject><subject>Proteins</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Time Factors</subject><subject>Tumors</subject><subject>Vaccination</subject><subject>Vaccines</subject><subject>Vaccines, DNA - chemistry</subject><subject>Vaccines, DNA - immunology</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</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>eNqFkU1r3DAQhkVpaT7aXxAogkJv3kqyLEvHZfO1ENIctr0aWx5ttKylrSQHfOlvjzbZJJBLTxpmnnnR8CB0RsmMEip-bmbTkO5hxgipcmdGqPqAjmnFqoIQxj--1lQcoZMYN7milRKf0REVnPKSqGP07_x2jv-0WlsHES-dDtBGwMthGJ1fg7Papgl7g5e99WnaWY1X4-ADnrtk8xx3E161YQ3JujW-9Q-wxZdjtN7hu-ATWBdx8i90cRcggntiF7Ddxi_ok2m3Eb4e3lP0-_Jitbgubn5dLRfzm0JzJVLBZccBoBeSGVnpmoLSxNT5vFoCL43uhWGsMrTvaiXzCFTPO1FLqXlHtClP0Y_n3F3wf0eIqRls1PkHrQM_xiajTFZS_hekNRV1SaoMfn8HbvwYXD4iM4pJIkpJMlU-Uzr4GAOYZhfs0IapoaTZW2w2zZPFZm9x38wW89a3Q_bYDdC_7Ry0vQGuTWOAV2BIOUYoVj4CoSClkQ</recordid><startdate>200604</startdate><enddate>200604</enddate><creator>Fredriksen, Agnete B</creator><creator>Sandlie, Inger</creator><creator>Bogen, Bjarne</creator><general>Elsevier Limited</general><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>7X7</scope><scope>7XB</scope><scope>88E</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>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200604</creationdate><title>DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells</title><author>Fredriksen, Agnete B ; Sandlie, Inger ; Bogen, Bjarne</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c496t-48b4eeed682f85c71e9c0f752578e43fcd6f225f1db798c0fe9d4b6788c4b0cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Animals</topic><topic>Antibodies</topic><topic>Antigen-Presenting Cells - immunology</topic><topic>Antigens</topic><topic>Antigens, Neoplasm - genetics</topic><topic>Antigens, Neoplasm - immunology</topic><topic>Chemokines</topic><topic>Dimerization</topic><topic>Electroporation</topic><topic>Gene therapy</topic><topic>Histocompatibility Antigens Class II - immunology</topic><topic>Immunoglobulin Idiotypes - genetics</topic><topic>Immunoglobulin Idiotypes - immunology</topic><topic>Injections, Intramuscular</topic><topic>Lymphocytes</topic><topic>Lymphoma</topic><topic>Lymphoma, B-Cell - immunology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, SCID</topic><topic>Mice, Transgenic</topic><topic>Models, Immunological</topic><topic>Multiple myeloma</topic><topic>Multiple Myeloma - immunology</topic><topic>Neoplasms, Experimental - immunology</topic><topic>Neoplasms, Experimental - prevention & control</topic><topic>Plasmids</topic><topic>Proteins</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>Vaccination</topic><topic>Vaccines</topic><topic>Vaccines, DNA - chemistry</topic><topic>Vaccines, DNA - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fredriksen, Agnete B</creatorcontrib><creatorcontrib>Sandlie, Inger</creatorcontrib><creatorcontrib>Bogen, Bjarne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fredriksen, Agnete B</au><au>Sandlie, Inger</au><au>Bogen, Bjarne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2006-04</date><risdate>2006</risdate><volume>13</volume><issue>4</issue><spage>776</spage><epage>785</epage><pages>776-785</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>Naked DNA vaccines have a number of advantages over conventional vaccines, but induce only weak immune responses. We have here investigated if this inadequacy may be overcome by inducing muscle to secrete fusion proteins with the ability to target antigen-presenting cells (APC). The novel targeted vaccines are homodimers with (i) two identical single-chain fragment variable (scFv) targeting units specific for MHC class II molecules on mouse APC, (ii) a human Ig hinge and C(H)3 dimerization unit, and (iii) two identical scFv tumor antigenic units (idiotypes) from B cell cancers. After plasmid injection and electroporation of mouse muscle, secreted vaccine proteins (vaccibodies) delivered idiotypic tumor antigen to APC in draining lymph nodes for induction of T and B cell responses that protected mice against tumor challenges with a multiple myeloma (MOPC315) and a B cell lymphoma (A20). Targeting to APC was essential for these effects. The results show that immunogenicity of plasmid DNA vaccines can be increased by inducing muscle to secrete proteins that target antigen to APC.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>16414309</pmid><doi>10.1016/j.ymthe.2005.10.019</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies Antigen-Presenting Cells - immunology Antigens Antigens, Neoplasm - genetics Antigens, Neoplasm - immunology Chemokines Dimerization Electroporation Gene therapy Histocompatibility Antigens Class II - immunology Immunoglobulin Idiotypes - genetics Immunoglobulin Idiotypes - immunology Injections, Intramuscular Lymphocytes Lymphoma Lymphoma, B-Cell - immunology Mice Mice, Inbred BALB C Mice, SCID Mice, Transgenic Models, Immunological Multiple myeloma Multiple Myeloma - immunology Neoplasms, Experimental - immunology Neoplasms, Experimental - prevention & control Plasmids Proteins Recombinant Fusion Proteins - immunology Time Factors Tumors Vaccination Vaccines Vaccines, DNA - chemistry Vaccines, DNA - immunology |
title | DNA Vaccines Increase Immunogenicity of Idiotypic Tumor Antigen by Targeting Novel Fusion Proteins to Antigen-Presenting Cells |
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