Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections
► Linkage of NT-gp96 to E7 led to increase IFN-γ level compared to E7 alone. ► Delivery of E7-NT-gp96 with PEI600-Tat was further protective against E7-expressing tumors. ► IP-10 co-delivery could additionally enhance the preventive effect of the E7-NT-gp96+ PEI600-Tat. ► RANTES co-administration al...
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| Veröffentlicht in: | Molecular immunology 2013-01, Vol.53 (1-2), p.149-160 |
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| creator | Mohit, Elham Bolhassani, Azam Zahedifard, Farnaz Seyed, Negar Eslamifar, Ali Taghikhani, Mohammad Samimi-Rad, Katayoun Rafati, Sima |
| description | ► Linkage of NT-gp96 to E7 led to increase IFN-γ level compared to E7 alone. ► Delivery of E7-NT-gp96 with PEI600-Tat was further protective against E7-expressing tumors. ► IP-10 co-delivery could additionally enhance the preventive effect of the E7-NT-gp96+ PEI600-Tat. ► RANTES co-administration along with E7-NT-gp96+ PEI600-Tat had overall detrimental effects on protection status against TC-1. ► In therapeutic experiment, co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivered by PEI600-Tat can significantly suppress TC-1 tumor growth.
Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers. |
| doi_str_mv | 10.1016/j.molimm.2012.07.011 |
| format | Article |
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Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.</description><identifier>ISSN: 0161-5890</identifier><identifier>EISSN: 1872-9142</identifier><identifier>DOI: 10.1016/j.molimm.2012.07.011</identifier><identifier>PMID: 22926003</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animal models ; Animals ; Cancer ; Chemokine CXCL10 - immunology ; Chemokines ; Data processing ; DNA vaccines ; Enzyme-Linked Immunosorbent Assay ; Female ; Fusion protein ; Gene Products, tat - pharmacology ; Gene transfer ; Gene Transfer Techniques ; glycoprotein gp96 ; gp96 ; HPV DNA vaccine ; Immunity ; Immunologic Factors - immunology ; Immunologic Factors - pharmacology ; Immunology ; Immunomodulation ; Immunomodulation - immunology ; Immunostimulation ; Infection ; Inoculation ; Interleukin 2 ; IP-10 ; IP-10 protein ; Life Sciences ; Lymph nodes ; Membrane Glycoproteins - immunology ; Membrane Glycoproteins - pharmacology ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental - prevention & control ; Neoplasms, Experimental - virology ; Papillomavirus E7 Proteins - immunology ; Papillomavirus E7 Proteins - pharmacology ; Papillomavirus Infections - prevention & control ; Papillomavirus Vaccines - immunology ; PEI600-Tat ; Polyethyleneimine - pharmacology ; RANTES ; Transfection ; Tumor cells ; Tumors ; Vaccines, DNA - immunology ; Vaccinology</subject><ispartof>Molecular immunology, 2013-01, Vol.53 (1-2), p.149-160</ispartof><rights>2012 Elsevier Ltd</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-3a3a03c88fc8471fa40bd197ceb98f21cdbbe71a337d4d7821e6bb2efda6abf63</citedby><cites>FETCH-LOGICAL-c433t-3a3a03c88fc8471fa40bd197ceb98f21cdbbe71a337d4d7821e6bb2efda6abf63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0161589012003586$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22926003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://riip.hal.science/pasteur-00789216$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohit, Elham</creatorcontrib><creatorcontrib>Bolhassani, Azam</creatorcontrib><creatorcontrib>Zahedifard, Farnaz</creatorcontrib><creatorcontrib>Seyed, Negar</creatorcontrib><creatorcontrib>Eslamifar, Ali</creatorcontrib><creatorcontrib>Taghikhani, Mohammad</creatorcontrib><creatorcontrib>Samimi-Rad, Katayoun</creatorcontrib><creatorcontrib>Rafati, Sima</creatorcontrib><title>Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections</title><title>Molecular immunology</title><addtitle>Mol Immunol</addtitle><description>► Linkage of NT-gp96 to E7 led to increase IFN-γ level compared to E7 alone. ► Delivery of E7-NT-gp96 with PEI600-Tat was further protective against E7-expressing tumors. ► IP-10 co-delivery could additionally enhance the preventive effect of the E7-NT-gp96+ PEI600-Tat. ► RANTES co-administration along with E7-NT-gp96+ PEI600-Tat had overall detrimental effects on protection status against TC-1. ► In therapeutic experiment, co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivered by PEI600-Tat can significantly suppress TC-1 tumor growth.
Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.</description><subject>Animal models</subject><subject>Animals</subject><subject>Cancer</subject><subject>Chemokine CXCL10 - immunology</subject><subject>Chemokines</subject><subject>Data processing</subject><subject>DNA vaccines</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Fusion protein</subject><subject>Gene Products, tat - pharmacology</subject><subject>Gene transfer</subject><subject>Gene Transfer Techniques</subject><subject>glycoprotein gp96</subject><subject>gp96</subject><subject>HPV DNA vaccine</subject><subject>Immunity</subject><subject>Immunologic Factors - immunology</subject><subject>Immunologic Factors - pharmacology</subject><subject>Immunology</subject><subject>Immunomodulation</subject><subject>Immunomodulation - immunology</subject><subject>Immunostimulation</subject><subject>Infection</subject><subject>Inoculation</subject><subject>Interleukin 2</subject><subject>IP-10</subject><subject>IP-10 protein</subject><subject>Life Sciences</subject><subject>Lymph nodes</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Neoplasms, Experimental - prevention & control</subject><subject>Neoplasms, Experimental - virology</subject><subject>Papillomavirus E7 Proteins - immunology</subject><subject>Papillomavirus E7 Proteins - pharmacology</subject><subject>Papillomavirus Infections - prevention & control</subject><subject>Papillomavirus Vaccines - immunology</subject><subject>PEI600-Tat</subject><subject>Polyethyleneimine - pharmacology</subject><subject>RANTES</subject><subject>Transfection</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Vaccines, DNA - immunology</subject><subject>Vaccinology</subject><issn>0161-5890</issn><issn>1872-9142</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU-P0zAQxS0EYkvhGyDkI5eEGTubPxekanehlSroYeFqOc5k6xLHJU6KKr48rrLsEU6Wxr_3ZvQeY28RUgTMPxxS5zvrXCoARQpFCojP2ALLQiQVZuI5W0QMk-uygiv2KoQDAOSQX79kV0JUIgeQC_Z749zUe-ebqdOjH86c2pbMGLhv-WaXIHCzJ-d_2J647nz_wH_Zcc93d5tokNzrkTfU2RNFZTiHkRy3Pb_9suInbYzt9Wh9z_WDtn0Y-Xr3PX5f_OM0vGYvWt0FevP4Ltm3T3f3N-tk-_Xz5ma1TUwm5ZhILTVIU5atKbMCW51B3WBVGKqrshVomrqmArWURZM1RSmQ8roW1DY613WbyyVLZt-97tRxsE4PZ-W1VevVVh11PHoaFEBRVgLzE0b-_cwfB_9zojAqZ4OhrtM9-SkoRJRCQC7L_6MgKwGQxayXLJtRM_gQBmqfTkFQl0bVQc2NqkujCgoVG42yd48bptpR8yT6W2EEPs4AxQhPlgYVjKXeUGOHGLRqvP33hj-wj7PA</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Mohit, Elham</creator><creator>Bolhassani, Azam</creator><creator>Zahedifard, Farnaz</creator><creator>Seyed, Negar</creator><creator>Eslamifar, Ali</creator><creator>Taghikhani, Mohammad</creator><creator>Samimi-Rad, Katayoun</creator><creator>Rafati, Sima</creator><general>Elsevier Ltd</general><general>Elsevier</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>7X8</scope><scope>7T5</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>1XC</scope></search><sort><creationdate>20130101</creationdate><title>Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections</title><author>Mohit, Elham ; Bolhassani, Azam ; Zahedifard, Farnaz ; Seyed, Negar ; Eslamifar, Ali ; Taghikhani, Mohammad ; Samimi-Rad, Katayoun ; Rafati, Sima</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-3a3a03c88fc8471fa40bd197ceb98f21cdbbe71a337d4d7821e6bb2efda6abf63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Cancer</topic><topic>Chemokine CXCL10 - immunology</topic><topic>Chemokines</topic><topic>Data processing</topic><topic>DNA vaccines</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Fusion protein</topic><topic>Gene Products, tat - pharmacology</topic><topic>Gene transfer</topic><topic>Gene Transfer Techniques</topic><topic>glycoprotein gp96</topic><topic>gp96</topic><topic>HPV DNA vaccine</topic><topic>Immunity</topic><topic>Immunologic Factors - immunology</topic><topic>Immunologic Factors - pharmacology</topic><topic>Immunology</topic><topic>Immunomodulation</topic><topic>Immunomodulation - immunology</topic><topic>Immunostimulation</topic><topic>Infection</topic><topic>Inoculation</topic><topic>Interleukin 2</topic><topic>IP-10</topic><topic>IP-10 protein</topic><topic>Life Sciences</topic><topic>Lymph nodes</topic><topic>Membrane Glycoproteins - immunology</topic><topic>Membrane Glycoproteins - pharmacology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Neoplasms, Experimental - prevention & control</topic><topic>Neoplasms, Experimental - virology</topic><topic>Papillomavirus E7 Proteins - immunology</topic><topic>Papillomavirus E7 Proteins - pharmacology</topic><topic>Papillomavirus Infections - prevention & control</topic><topic>Papillomavirus Vaccines - immunology</topic><topic>PEI600-Tat</topic><topic>Polyethyleneimine - pharmacology</topic><topic>RANTES</topic><topic>Transfection</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Vaccines, DNA - immunology</topic><topic>Vaccinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mohit, Elham</creatorcontrib><creatorcontrib>Bolhassani, Azam</creatorcontrib><creatorcontrib>Zahedifard, Farnaz</creatorcontrib><creatorcontrib>Seyed, Negar</creatorcontrib><creatorcontrib>Eslamifar, Ali</creatorcontrib><creatorcontrib>Taghikhani, Mohammad</creatorcontrib><creatorcontrib>Samimi-Rad, Katayoun</creatorcontrib><creatorcontrib>Rafati, Sima</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Molecular immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mohit, Elham</au><au>Bolhassani, Azam</au><au>Zahedifard, Farnaz</au><au>Seyed, Negar</au><au>Eslamifar, Ali</au><au>Taghikhani, Mohammad</au><au>Samimi-Rad, Katayoun</au><au>Rafati, Sima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections</atitle><jtitle>Molecular immunology</jtitle><addtitle>Mol Immunol</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>53</volume><issue>1-2</issue><spage>149</spage><epage>160</epage><pages>149-160</pages><issn>0161-5890</issn><eissn>1872-9142</eissn><abstract>► Linkage of NT-gp96 to E7 led to increase IFN-γ level compared to E7 alone. ► Delivery of E7-NT-gp96 with PEI600-Tat was further protective against E7-expressing tumors. ► IP-10 co-delivery could additionally enhance the preventive effect of the E7-NT-gp96+ PEI600-Tat. ► RANTES co-administration along with E7-NT-gp96+ PEI600-Tat had overall detrimental effects on protection status against TC-1. ► In therapeutic experiment, co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivered by PEI600-Tat can significantly suppress TC-1 tumor growth.
Although DNA vaccines represent an attractive approach for generating antigen-specific immunity, improvement of their potency is highly demanded. In the present study, three strategies including linkage to immunostimulatory molecules (N-terminal of gp96), co-administration of chemokines (IP-10 or RANTES) and PEI600-Tat as non-viral gene delivery system have been applied to enhance DNA vaccine efficacy against HPV infections. We found that C57BL/6 immunization with E7-NT-gp96 fusion gene led to increased level of IFN-γ compared to E7 alone. The fused genes showed considerable protective potency in tumor mice model. In addition, E7-NT-gp96 delivered with PEI600-Tat was more protective against E7-expressing tumors comparing with E7-NT-gp96 alone. Our results showed that co-administration of IP-10 with E7-NT-gp96 delivered by PEI600-Tat elicits significant IFN-γ production and consequently a strong preventive response against TC-1 tumor cells in contrast to increased tumor growth by RANTES co-delivery. Also in therapeutic experiment, our data showed that co-immunization of IP-10 at the same inoculation site of TC-1 along with E7-NT-gp96 delivery by PEI600-Tat is able to significantly suppress TC-1 tumor growth. The successful treatment by this immunization protocol was associated with the elevated levels of IFN-γ and IL-2 production in the lymph nodes. These data indicated that fusion of NT-gp96 to E7 in combination with IP-10 co-administration and PEI600-Tat delivery system can synergistically enhance the potency of HPV DNA vaccines. Therefore, this approach suggests a combinational therapeutic strategy against cervical and other HPV-related cancers.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>22926003</pmid><doi>10.1016/j.molimm.2012.07.011</doi><tpages>12</tpages></addata></record> |
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| ispartof | Molecular immunology, 2013-01, Vol.53 (1-2), p.149-160 |
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| subjects | Animal models Animals Cancer Chemokine CXCL10 - immunology Chemokines Data processing DNA vaccines Enzyme-Linked Immunosorbent Assay Female Fusion protein Gene Products, tat - pharmacology Gene transfer Gene Transfer Techniques glycoprotein gp96 gp96 HPV DNA vaccine Immunity Immunologic Factors - immunology Immunologic Factors - pharmacology Immunology Immunomodulation Immunomodulation - immunology Immunostimulation Infection Inoculation Interleukin 2 IP-10 IP-10 protein Life Sciences Lymph nodes Membrane Glycoproteins - immunology Membrane Glycoproteins - pharmacology Mice Mice, Inbred C57BL Neoplasms, Experimental - prevention & control Neoplasms, Experimental - virology Papillomavirus E7 Proteins - immunology Papillomavirus E7 Proteins - pharmacology Papillomavirus Infections - prevention & control Papillomavirus Vaccines - immunology PEI600-Tat Polyethyleneimine - pharmacology RANTES Transfection Tumor cells Tumors Vaccines, DNA - immunology Vaccinology |
| title | Immunomodulatory effects of IP-10 chemokine along with PEI600-Tat delivery system in DNA vaccination against HPV infections |
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