CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model
Background DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is...
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| Veröffentlicht in: | The journal of gene medicine 2012-02, Vol.14 (2), p.128-137 |
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| creator | Nguyen-Hoai, Tam Baldenhofer, Gerd Ahmed, Mona Sayed Pham-Duc, Minh Gries, Margarete Lipp, Martin Dörken, Bernd Pezzutto, Antonio Westermann, Jörg |
| description | Background
DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.
Methods
pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.
Results
Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.
Conclusions
CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd. |
| doi_str_mv | 10.1002/jgm.1651 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_922763085</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3918844771</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3861-9a0817c67d426a3a040760613111323d7ef75133c1c59a0de0aebf60a3793d6c3</originalsourceid><addsrcrecordid>eNp10Utv1DAQB_AIgegDJD4BssSBckjrsWM7PrZp2aUKRUjLQ1ws15lFXvJY7GRh-fS42m0PSPhiy_PTX6OZLHsB9BQoZWer790pSAGPskMQDHLGRPE4vanWeaHLrwfZUYwrSkGVpX6aHbB0SqHhMNtUVQ2anFzV1Rviu3UYNhjJYg75emht8H-wSd_d1CMJGNdDH1PZ9g1JckQ3-g3u6n7cEt8TS7op-KTnGNhZjxO5vDknG-uc7-3oh550Q4Pts-zJ0rYRn-_v4-zT26tFNc_rD7N31XmdO15KyLWlJSgnVVMwabmlBVWSSuAAwBlvFC6VAM4dOJFsg9Ti7VJSy5XmjXT8OHu9y03t_pwwjqbz0WHb2h6HKRrNmJKcliLJV__I1TCFPjVnQAmhi0IVOqmTnXJhiDHg0qyD72zYGqDmbhUmrcLcrSLRl_vA6bbD5gHezz6BfAd--Ra3_w0y17P3-8C993HE3w_ehh9GKq6E-XIzM-Jj_W3x-UKbC_4XHwifGQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1755944749</pqid></control><display><type>article</type><title>CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Nguyen-Hoai, Tam ; Baldenhofer, Gerd ; Ahmed, Mona Sayed ; Pham-Duc, Minh ; Gries, Margarete ; Lipp, Martin ; Dörken, Bernd ; Pezzutto, Antonio ; Westermann, Jörg</creator><creatorcontrib>Nguyen-Hoai, Tam ; Baldenhofer, Gerd ; Ahmed, Mona Sayed ; Pham-Duc, Minh ; Gries, Margarete ; Lipp, Martin ; Dörken, Bernd ; Pezzutto, Antonio ; Westermann, Jörg</creatorcontrib><description>Background
DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.
Methods
pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.
Results
Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.
Conclusions
CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd.</description><identifier>ISSN: 1099-498X</identifier><identifier>EISSN: 1521-2254</identifier><identifier>DOI: 10.1002/jgm.1651</identifier><identifier>PMID: 22228591</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Animals ; CCL19 ; Chemokine CCL19 - immunology ; Chemokine CCL19 - metabolism ; chemokines ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; DNA vaccination ; ELC ; Enzyme-Linked Immunospot Assay ; Female ; Gene therapy ; Her2/neu ; Mice ; Mice, Inbred BALB C ; Neoplasms - prevention & control ; Plasmids - genetics ; Receptor, ErbB-2 - genetics ; Receptors, CCR7 - immunology ; Receptors, CCR7 - metabolism ; Th1 Cells - immunology ; Th1 Cells - metabolism ; Vaccination ; Vaccines, DNA - genetics ; Vaccines, DNA - immunology</subject><ispartof>The journal of gene medicine, 2012-02, Vol.14 (2), p.128-137</ispartof><rights>Copyright © 2012 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3861-9a0817c67d426a3a040760613111323d7ef75133c1c59a0de0aebf60a3793d6c3</citedby><cites>FETCH-LOGICAL-c3861-9a0817c67d426a3a040760613111323d7ef75133c1c59a0de0aebf60a3793d6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjgm.1651$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjgm.1651$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22228591$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nguyen-Hoai, Tam</creatorcontrib><creatorcontrib>Baldenhofer, Gerd</creatorcontrib><creatorcontrib>Ahmed, Mona Sayed</creatorcontrib><creatorcontrib>Pham-Duc, Minh</creatorcontrib><creatorcontrib>Gries, Margarete</creatorcontrib><creatorcontrib>Lipp, Martin</creatorcontrib><creatorcontrib>Dörken, Bernd</creatorcontrib><creatorcontrib>Pezzutto, Antonio</creatorcontrib><creatorcontrib>Westermann, Jörg</creatorcontrib><title>CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model</title><title>The journal of gene medicine</title><addtitle>J Gene Med</addtitle><description>Background
DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.
Methods
pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.
Results
Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.
Conclusions
CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd.</description><subject>Animals</subject><subject>CCL19</subject><subject>Chemokine CCL19 - immunology</subject><subject>Chemokine CCL19 - metabolism</subject><subject>chemokines</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>DNA vaccination</subject><subject>ELC</subject><subject>Enzyme-Linked Immunospot Assay</subject><subject>Female</subject><subject>Gene therapy</subject><subject>Her2/neu</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neoplasms - prevention & control</subject><subject>Plasmids - genetics</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptors, CCR7 - immunology</subject><subject>Receptors, CCR7 - metabolism</subject><subject>Th1 Cells - immunology</subject><subject>Th1 Cells - metabolism</subject><subject>Vaccination</subject><subject>Vaccines, DNA - genetics</subject><subject>Vaccines, DNA - immunology</subject><issn>1099-498X</issn><issn>1521-2254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10Utv1DAQB_AIgegDJD4BssSBckjrsWM7PrZp2aUKRUjLQ1ws15lFXvJY7GRh-fS42m0PSPhiy_PTX6OZLHsB9BQoZWer790pSAGPskMQDHLGRPE4vanWeaHLrwfZUYwrSkGVpX6aHbB0SqHhMNtUVQ2anFzV1Rviu3UYNhjJYg75emht8H-wSd_d1CMJGNdDH1PZ9g1JckQ3-g3u6n7cEt8TS7op-KTnGNhZjxO5vDknG-uc7-3oh550Q4Pts-zJ0rYRn-_v4-zT26tFNc_rD7N31XmdO15KyLWlJSgnVVMwabmlBVWSSuAAwBlvFC6VAM4dOJFsg9Ti7VJSy5XmjXT8OHu9y03t_pwwjqbz0WHb2h6HKRrNmJKcliLJV__I1TCFPjVnQAmhi0IVOqmTnXJhiDHg0qyD72zYGqDmbhUmrcLcrSLRl_vA6bbD5gHezz6BfAd--Ra3_w0y17P3-8C993HE3w_ehh9GKq6E-XIzM-Jj_W3x-UKbC_4XHwifGQ</recordid><startdate>201202</startdate><enddate>201202</enddate><creator>Nguyen-Hoai, Tam</creator><creator>Baldenhofer, Gerd</creator><creator>Ahmed, Mona Sayed</creator><creator>Pham-Duc, Minh</creator><creator>Gries, Margarete</creator><creator>Lipp, Martin</creator><creator>Dörken, Bernd</creator><creator>Pezzutto, Antonio</creator><creator>Westermann, Jörg</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Periodicals Inc</general><scope>BSCLL</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>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201202</creationdate><title>CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model</title><author>Nguyen-Hoai, Tam ; Baldenhofer, Gerd ; Ahmed, Mona Sayed ; Pham-Duc, Minh ; Gries, Margarete ; Lipp, Martin ; Dörken, Bernd ; Pezzutto, Antonio ; Westermann, Jörg</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3861-9a0817c67d426a3a040760613111323d7ef75133c1c59a0de0aebf60a3793d6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>CCL19</topic><topic>Chemokine CCL19 - immunology</topic><topic>Chemokine CCL19 - metabolism</topic><topic>chemokines</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>DNA vaccination</topic><topic>ELC</topic><topic>Enzyme-Linked Immunospot Assay</topic><topic>Female</topic><topic>Gene therapy</topic><topic>Her2/neu</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neoplasms - prevention & control</topic><topic>Plasmids - genetics</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptors, CCR7 - immunology</topic><topic>Receptors, CCR7 - metabolism</topic><topic>Th1 Cells - immunology</topic><topic>Th1 Cells - metabolism</topic><topic>Vaccination</topic><topic>Vaccines, DNA - genetics</topic><topic>Vaccines, DNA - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nguyen-Hoai, Tam</creatorcontrib><creatorcontrib>Baldenhofer, Gerd</creatorcontrib><creatorcontrib>Ahmed, Mona Sayed</creatorcontrib><creatorcontrib>Pham-Duc, Minh</creatorcontrib><creatorcontrib>Gries, Margarete</creatorcontrib><creatorcontrib>Lipp, Martin</creatorcontrib><creatorcontrib>Dörken, Bernd</creatorcontrib><creatorcontrib>Pezzutto, Antonio</creatorcontrib><creatorcontrib>Westermann, Jörg</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>The journal of gene medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nguyen-Hoai, Tam</au><au>Baldenhofer, Gerd</au><au>Ahmed, Mona Sayed</au><au>Pham-Duc, Minh</au><au>Gries, Margarete</au><au>Lipp, Martin</au><au>Dörken, Bernd</au><au>Pezzutto, Antonio</au><au>Westermann, Jörg</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model</atitle><jtitle>The journal of gene medicine</jtitle><addtitle>J Gene Med</addtitle><date>2012-02</date><risdate>2012</risdate><volume>14</volume><issue>2</issue><spage>128</spage><epage>137</epage><pages>128-137</pages><issn>1099-498X</issn><eissn>1521-2254</eissn><abstract>Background
DNA vaccination is an attractive approach for tumor vaccination because plasmid DNA (pDNA) can be used as a ‘general vaccine’ across major histocompatibility complex barriers. Coexpression of immunomodulatory molecules can help to amplify the immunogenicity of DNA vaccines. CCL19 (ELC) is a CC chemokine with immunoregulatory properties, binding to the chemokine receptor CCR7 that is expressed on dendritic cells (DCs) and T cells. In vivo, CCL19 is a key regulator for the interactions between DCs and T cells in regional lymph nodes.
Methods
pDNA encoding Her2/neu and CCL19 was used as an intramuscular vaccine. Vaccination was performed in BALB/c mice, which were subsequently challenged with syngeneic Her2/neu+ tumor cells. Groups of mice were immunized with pDNA(Her2/neu) plus pDNA(CCL19), pDNA(Her2/neu) plus pDNA(CCL19) plus pDNA(GM‐CSF), pDNA(Her2/neu) plus pDNA(GM‐CSF), pDNA(Her2/neu), pDNA(CCL19), pDNA(GM‐CSF) or mock vector. Tumor protection by the vaccine and immune responses were monitored.
Results
Coadministration of pDNA(Her2/neu) and pDNA(CCL19) led to substantial improvement of tumor protection by the vaccine and induced a TH1‐polarized, Her2/neu‐specific immune response. Forty‐seven days after the tumor challenge, 58% of the mice coinjected with pDNA(Her2/neu) and pDNA(CCL19) remained tumor‐free compared to 22% after vaccination with pDNA(Her2/neu) alone. Additional administration of pDNA(GM‐CSF) led to further improvement of tumor protection and an amplification of Her2/neu‐specific immune responses.
Conclusions
CCL19 is able to induce a TH‐1 polarization of the anti‐Her2/neu immune response, which can be further amplified by granulocyte macrophage‐colony‐stimulating factor (GM‐CSF). Clinical use of a pDNA(Her2/neu‐CCL19 ± GM‐CSF) vaccine might be promising in Her2/neu + breast cancer in the clinical situation of minimal residual disease. Copyright © 2012 John Wiley & Sons, Ltd.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>22228591</pmid><doi>10.1002/jgm.1651</doi><tpages>10</tpages></addata></record> |
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| ispartof | The journal of gene medicine, 2012-02, Vol.14 (2), p.128-137 |
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| subjects | Animals CCL19 Chemokine CCL19 - immunology Chemokine CCL19 - metabolism chemokines Dendritic Cells - immunology Dendritic Cells - metabolism DNA vaccination ELC Enzyme-Linked Immunospot Assay Female Gene therapy Her2/neu Mice Mice, Inbred BALB C Neoplasms - prevention & control Plasmids - genetics Receptor, ErbB-2 - genetics Receptors, CCR7 - immunology Receptors, CCR7 - metabolism Th1 Cells - immunology Th1 Cells - metabolism Vaccination Vaccines, DNA - genetics Vaccines, DNA - immunology |
| title | CCL19 (ELC) improves TH1-polarized immune responses and protective immunity in a murine Her2/neu DNA vaccination model |
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